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Sample records for adult mouse offspring

  1. Maternal high-protein diet during pregnancy, but not during suckling, induced altered expression of an increasing number of hepatic genes in adult mouse offspring.

    Science.gov (United States)

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Metges, Cornelia C

    2016-04-01

    Indirect effects of a high-protein maternal diet are not well understood. In this study, we analyzed short-term and sustainable effects of a prenatal versus early postnatal maternal high-protein diet on growth and hepatic gene expression in mouse offspring. Dams were exposed to an isoenergetic high-protein (HP, 40 % w/w) diet during pregnancy or lactation. Growth and hepatic expression profiles of male offspring were evaluated directly after weaning and 150 days after birth. Offspring from two dietary groups, high-protein diet during pregnancy and control diet during lactation (HPC), and control diet during pregnancy and high-protein diet during lactation (CHP), were compared with offspring (CC) from control-fed dams. Maternal CHP treatment was associated with sustained offspring growth retardation, but decreased numbers of affected hepatic genes in adults compared to weanlings. In contrast, offspring of the HPC group did not show persistent effects on growth parameters, but the number of affected hepatic genes was even increased at adult age. In both dietary groups, however, only a small subset of genes was affected in weanlings as well as in adults. We conclude that (1) prenatal and early postnatal maternal HP diet caused persistent, but (2) different effects and partially complementary trends on growth characteristics and on the hepatic transcriptome and associated pathways and that (3) only a small number of genes and associated upstream regulators might be involved in passing early diet-induced imprints to adulthood.

  2. Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

    2016-11-22

    During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

  3. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    Science.gov (United States)

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  4. Constraints on the adult-offspring size relationship in protists.

    Science.gov (United States)

    Caval-Holme, Franklin; Payne, Jonathan; Skotheim, Jan M

    2013-12-01

    The relationship between adult and offspring size is an important aspect of reproductive strategy. Although this filial relationship has been extensively examined in plants and animals, we currently lack comparable data for protists, whose strategies may differ due to the distinct ecological and physiological constraints on single-celled organisms. Here, we report measurements of adult and offspring sizes in 3888 species and subspecies of foraminifera, a class of large marine protists. Foraminifera exhibit a wide range of reproductive strategies; species of similar adult size may have offspring whose sizes vary 100-fold. Yet, a robust pattern emerges. The minimum (5th percentile), median, and maximum (95th percentile) offspring sizes exhibit a consistent pattern of increase with adult size independent of environmental change and taxonomic variation over the past 400 million years. The consistency of this pattern may arise from evolutionary optimization of the offspring size-fecundity trade-off and/or from cell-biological constraints that limit the range of reproductive strategies available to single-celled organisms. When compared with plants and animals, foraminifera extend the evidence that offspring size covaries with adult size across an additional five orders of magnitude in organism size. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  5. Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring.

    Science.gov (United States)

    Sellayah, Dyan; Dib, Lea; Anthony, Frederick W; Watkins, Adam J; Fleming, Tom P; Hanson, Mark A; Cagampang, Felino R

    2014-10-01

    Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Female MF-1 mice were fed a normal protein (NP, 18% casein) or a protein-restricted (PR, 9% casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45% kcal fat) or standard chow (C, 7% kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7-11 per group). PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.

  6. Cognitive function in adult offspring of women with Type 1 diabetes

    DEFF Research Database (Denmark)

    Clausen, Tine Dalsgaard; Mortensen, E L; Schmidt, L

    2011-01-01

    Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes.......Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes....

  7. Maternal folate depletion and high-fat feeding from weaning affects DNA methylation and DNA repair in brain of adult offspring.

    Science.gov (United States)

    Langie, Sabine A S; Achterfeldt, Sebastian; Gorniak, Joanna P; Halley-Hogg, Kirstin J A; Oxley, David; van Schooten, Frederik J; Godschalk, Roger W L; McKay, Jill A; Mathers, John C

    2013-08-01

    The mechanisms through which environmental and dietary factors modulate DNA repair are still unclear but may include dysregulation of gene expression due to altered epigenetic markings. In a mouse model, we investigated the effect of maternal folate depletion during pregnancy and lactation, and high-fat feeding from weaning, on base excision repair (BER) and DNA methylation and expression of selected BER-related genes in the brain of adult offspring. While folate depletion did not affect BER activity of the mothers, BER increased in the offspring at weaning (P=0.052). In the long term, as observed in 6-mo-old offspring, the double insult, i.e., maternal low-folate supply and high-fat feeding from weaning, decreased BER activity significantly in the cortex, cerebellum, hippocampus, and subcortical regions (P≤0.017). This fall in BER activity was associated with small changes in methylation or expression of BER-related genes. Maternal folate depletion led to slightly increased oxidative DNA damage levels in subcortical regions of adult offspring, which may increase sensitivity to oxidative stress and predispose to neurological disorders. In summary, our data suggest that low-folate supply during early life may leave an epigenetic mark that can predispose the offspring to further dietary insults, causing adverse effects during adult life.

  8. Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring.

    Science.gov (United States)

    Walton, Sarah L; Singh, Reetu R; Tan, Tiffany; Paravicini, Tamara M; Moritz, Karen M

    2016-03-01

    Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  9. Micro-Albuminuria In Adolescent/Young Adult Offsprings Of ...

    African Journals Online (AJOL)

    young adult offsprings of Nigeria hypertensive adults. Background: On the premise that micro-albuminuria is a predictor of early stage hypertensive disease and the fact that heredity plays an important role in the aetiology of essential hypertension, ...

  10. Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

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    Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

    2017-12-01

    Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

  11. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    Science.gov (United States)

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.

    Science.gov (United States)

    Strobl, Marie-Therese J; Freeman, Daniel; Patel, Jenica; Poulsen, Ryan; Wendler, Christopher C; Rivkees, Scott A; Coleman, Jason E

    2017-05-01

    Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring.

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    Dembele, Korami; Yao, Xing-Hai; Chen, Li; Nyomba, B L Grégoire

    2006-09-01

    Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by increased appetite, catch-up growth, insulin resistance, and impaired glucose tolerance in the rat offspring. Because EtOH can induce oxidative stress, which is a putative mechanism of insulin resistance, and because of the central role of the hypothalamus in the regulation of energy homeostasis and insulin action, we investigated whether prenatal EtOH exposure causes oxidative damage to the hypothalamus, which may alter its function. Female rats were given EtOH by gavage throughout pregnancy. At birth, their offspring were smaller than those of non-EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7 (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal EtOH exposure was associated with decreased levels of glutathione and increased expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH-exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC protein concentration. Thus only adult offspring preexposed to EtOH had increased hypothalamic tissue damage and decreased levels of POMC, which could impair melanocortin signaling. We conclude that prenatal EtOH exposure causes hypothalamic oxidative stress, which persists into adult life and alters melanocortin action during adulthood. These neuroendocrine alterations may explain weight gain and insulin resistance in rats exposed to EtOH early in life.

  14. Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring.

    Science.gov (United States)

    Bolton, Jessica L; Auten, Richard L; Bilbo, Staci D

    2014-03-01

    Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1β response to an LPS challenge at postnatal day (P)30, whereas their central IL-1β response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Maternal hyperthyroidism increases the susceptibility of rat adult offspring to cardiovascular disorders.

    Science.gov (United States)

    Lino, Caroline A; da Silva, Ivson Bezerra; Shibata, Caroline E R; Monteiro, Priscilla de S; Barreto-Chaves, Maria Luiza M

    2015-11-15

    Suboptimal intrauterine conditions as changed hormone levels during critical periods of the development are considered an insult and implicate in physiological adaptations which may result in pathological outcomes in later life. This study evaluated the effect of maternal hyperthyroidism (hyper) on cardiac function in adult offspring and the possible involvement of cardiac Renin-Angiotensin System (RAS) in this process. Wistar dams received orally thyroxin (12 mg/L) from gestational day 9 (GD9) until GD18. Adult offspring at postnatal day 90 (PND90) from hyper dams presented increased SBP evaluated by plethysmography and worse recovery after ischemia-reperfusion (I/R), as evidenced by decreased LVDP, +dP/dT and -dP/dT at 25 min of reperfusion and by increased infarct size. Increased cardiac Angiotensin I/II levels and AT1R in hyper offspring were verified. Herein, we provide evidences that maternal hyperthyroidism leads to altered expression of RAS components in adult offspring, which may be correlated with worse recovery of the cardiac performance after ischemic insults and hypertension. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-01-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  17. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

    Science.gov (United States)

    Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

    2018-05-02

    Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

  18. Healthy offspring from freeze-dried mouse spermatozoa held on the International Space Station for 9 months.

    Science.gov (United States)

    Wakayama, Sayaka; Kamada, Yuko; Yamanaka, Kaori; Kohda, Takashi; Suzuki, Hiromi; Shimazu, Toru; Tada, Motoki N; Osada, Ikuko; Nagamatsu, Aiko; Kamimura, Satoshi; Nagatomo, Hiroaki; Mizutani, Eiji; Ishino, Fumitoshi; Yano, Sachiko; Wakayama, Teruhiko

    2017-06-06

    If humans ever start to live permanently in space, assisted reproductive technology using preserved spermatozoa will be important for producing offspring; however, radiation on the International Space Station (ISS) is more than 100 times stronger than that on Earth, and irradiation causes DNA damage in cells and gametes. Here we examined the effect of space radiation on freeze-dried mouse spermatozoa held on the ISS for 9 mo at -95 °C, with launch and recovery at room temperature. DNA damage to the spermatozoa and male pronuclei was slightly increased, but the fertilization and birth rates were similar to those of controls. Next-generation sequencing showed only minor genomic differences between offspring derived from space-preserved spermatozoa and controls, and all offspring grew to adulthood and had normal fertility. Thus, we demonstrate that although space radiation can damage sperm DNA, it does not affect the production of viable offspring after at least 9 mo of storage on the ISS.

  19. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring.

    Science.gov (United States)

    Watkins, Adam J; Wilkins, Adrian; Cunningham, Colm; Perry, V Hugh; Seet, Meei J; Osmond, Clive; Eckert, Judith J; Torrens, Christopher; Cagampang, Felino R A; Cleal, Jane; Gray, William P; Hanson, Mark A; Fleming, Tom P

    2008-04-15

    Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P size or nephron number was altered by diet treatment (P < 0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome.

  20. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    Science.gov (United States)

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (≥1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

  1. Young adult's attachment style as a partial mediator between maternal functioning and young adult offsprings' functioning.

    Science.gov (United States)

    Ruiz, Sarah K; Harris, Susan J; Martinez, Pedro; Gold, Philip M; Klimes-Dougan, Bonnie

    2018-05-01

    The quality of our early attachment relationships with primary caregivers is carried forward to new developmental domains, including interpersonal contexts in adulthood. One of the factors that can disrupt early attachment is maternal depression, which may be associated with less responsive care and may impede the development of a secure attachment. Moreover, this disruption in secure attachment may act as a mechanism by which offspring of depressed mothers are more likely to experience their own psychopathology. In this study we predicted that attachment anxiety and avoidance would mediate the relationship between maternal depression diagnosis and functional impairment predicting young adult offspring's functional impairment. This study utilized longitudinal data from 98 families with clinically diagnosed depressed and well mothers, and two of their young adult children, an older and younger sibling (N = 123, Female = 75, Mage = 22.09, SD = 2.57). Mother's and young adult children's functioning was based on clinical ratings on the Global Assessment Scale. Attachment was based on the young adult's self-report on the Experiences in Close Relationships. Results indicate that maternal diagnosis and functional impairment predicted offspring's functional impairment. This relationship was partially mediated through offspring's attachment anxiety, but not attachment avoidance. The mediator and outcome variable were measured concurrently, thus causal implications are limited. Our study provides critical evidence that early experiences with depressed mothers may have influence into young adulthood in typical and atypical domains of development. This work extends our understanding of the impact of early experiences in long-term development, and may have treatment implications for intervening on both maternal and romantic relationships to improve attachment. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice.

    Science.gov (United States)

    Khalyfa, Abdelnaby; Cortese, Rene; Qiao, Zhuanhong; Ye, Honggang; Bao, Riyue; Andrade, Jorge; Gozal, David

    2017-04-15

    Late gestation during pregnancy has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia, a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis and metabolic function in offspring. Here we show that late gestation intermittent hypoxia induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in visceral white adipose tissue. Fetal perturbations by OSA during pregnancy impose long-term detrimental effects manifesting as metabolic dysfunction in adult male offspring. Pregnancy, particularly late gestation (LG), has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesized that IH during late pregnancy (LG-IH) may increase the propensity for metabolic dysregulation and obesity in adult offspring via epigenetic modifications. Time-pregnant female C57BL/6 mice were exposed to LG-IH or room air (LG-RA) during days 13-18 of gestation. At 24 weeks, blood samples were collected from offspring mice for lipid profiles and insulin resistance, indirect calorimetry was performed and visceral white adipose tissues (VWAT) were assessed for inflammatory cells as well as for differentially methylated gene regions (DMRs) using a methylated DNA immunoprecipitation on chip (MeDIP-chip). Body weight, food intake, adiposity index, fasting insulin, triglycerides and cholesterol levels were all significantly higher in LG-IH male but not female offspring. LG-IH also altered metabolic expenditure and locomotor activities in male offspring, and increased number of pro-inflammatory macrophages emerged in VWAT along with 1520 DMRs (P < 0.0001), associated with 693

  3. Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence.

    Science.gov (United States)

    Thompson, Ronald G; Alonzo, Dana; Hasin, Deborah S

    2013-01-01

    This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems.

  4. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

    Science.gov (United States)

    Manti, Maria; Fornes, Romina; Qi, Xiaojuan; Folmerz, Elin; Lindén Hirschberg, Angelica; de Castro Barbosa, Thais; Maliqueo, Manuel; Benrick, Anna; Stener-Victorin, Elisabet

    2018-03-22

    Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

  5. Parental divorce, parental depression, and gender differences in adult offspring suicide attempt.

    Science.gov (United States)

    Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

    2009-12-01

    Research suggests parental divorce during childhood increases risk of suicide attempt for male but not female offspring. The negative impact on offspring associated with parental divorce may be better explained by parental psychopathology, such as depression. We examined whether adult offspring of parental divorce experience elevated risk of suicide attempt, controlling for parental history of depression, and whether the risk varies by the gender of the offspring. Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the sample consists of respondents who experienced parental divorce (N = 4895). Multivariable regressions controlled for age, race/ethnicity, income, marital status, and parental history of depression. Females living with their fathers were significantly more likely to report lifetime suicide attempts than females living with their mothers, even after controlling for parental depression. Findings suggest that childhood/adolescent parental divorce may have a stronger impact on suicide attempt risk in female offspring than previously recognized.

  6. Cognitive function in adult offspring of women with gestational diabetes-the role of glucose and other factors

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mortensen, Erik Lykke; Schmidt, Lone

    2013-01-01

    We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.......We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values....

  7. A general model for the scaling of offspring size and adult size.

    Science.gov (United States)

    Falster, Daniel S; Moles, Angela T; Westoby, Mark

    2008-09-01

    Understanding evolutionary coordination among different life-history traits is a key challenge for ecology and evolution. Here we develop a general quantitative model predicting how offspring size should scale with adult size by combining a simple model for life-history evolution with a frequency-dependent survivorship model. The key innovation is that larger offspring are afforded three different advantages during ontogeny: higher survivorship per time, a shortened juvenile phase, and advantage during size-competitive growth. In this model, it turns out that size-asymmetric advantage during competition is the factor driving evolution toward larger offspring sizes. For simplified and limiting cases, the model is shown to produce the same predictions as the previously existing theory on which it is founded. The explicit treatment of different survival advantages has biologically important new effects, mainly through an interaction between total maternal investment in reproduction and the duration of competitive growth. This goes on to explain alternative allometries between log offspring size and log adult size, as observed in mammals (slope = 0.95) and plants (slope = 0.54). Further, it suggests how these differences relate quantitatively to specific biological processes during recruitment. In these ways, the model generalizes across previous theory and provides explanations for some differences between major taxa.

  8. Insulin Resistance and Impaired Pancreatic β-Cell Function in Adult Offspring of Women With Diabetes in Pregnancy

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Damm, Peter; Mathiesen, Elisabeth R

    2013-01-01

    Context:Offspring of women with diabetes during pregnancy have increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate effects of intrauterine hyperglycemia on insulin secretion and - action in adult offspring of mothers...... a standard oral glucose tolerance test (120 minutes, 75 gram glucose). Pancreatic beta-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices.Results:Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes.......005).Conclusion:Reduced insulin sensitivity as well as impaired pancreatic beta cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy....

  9. Association between parental psychopathology and suicidal behavior among adult offspring: results from the cross-sectional South African Stress and Health survey

    Science.gov (United States)

    2014-01-01

    Background Prior studies have demonstrated a link between parental psychopathology and offspring suicidal behavior. However, it remains unclear what aspects of suicidal behavior among adult offspring are predicted by specific parental mental disorders, especially in Africa. This study set out to investigate the association between parental psychopathology and suicidal behavior among their adult offspring in a South African general population sample. Method Parental psychopathology and suicidal behavior in offspring were assessed using structured interviews among 4,315 respondents from across South Africa. The WHO CIDI was used to collect data on suicidal behavior, while the Family History Research Diagnostic Criteria Interview was used to assess prior parental psychopathology. Bivariate and multivariate survival models tested the associations between the type and number parental mental disorders (including suicide) and lifetime suicidal behavior in the offspring. Associations between a range of parental disorders and the onset of subsequent suicidal behavior (suicidal ideation, plans, and attempts) among adult offspring were tested. Results The presence of parental psychopathology significantly increased the odds of suicidal behavior among their adult offspring. More specifically, parental panic disorder was associated with offspring suicidal ideation, while parental panic disorder, generalized anxiety disorder and suicide were significantly associated with offspring suicide attempts. Among those with suicidal ideation, none of the tested forms of parental psychopathology was associated with having suicide plans or attempts. There was a dose–response relationship between the number of parental disorders and odds of suicidal ideation. Conclusions Parental psychopathology increases the odds of suicidal behavior among their adult offspring in the South African context, replicating results found in other regions. Specific parental disorders predicted the onset and

  10. Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring.

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    Michelle Lane

    Full Text Available Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2, which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity.

  11. Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

    Science.gov (United States)

    Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

    2013-03-01

    Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

  12. Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

    Science.gov (United States)

    Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-02-01

    Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

    Science.gov (United States)

    Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

    2015-01-01

    Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment.

    Science.gov (United States)

    Gao, Ling; Zhao, Yi-Chao; Liang, Yan; Lin, Xian-Hua; Tan, Ya-Jing; Wu, Dan-Dan; Li, Xin-Zhu; Ye, Bo-Zhi; Kong, Fan-Qi; Sheng, Jian-Zhong; Huang, He-Feng

    2016-10-01

    Diabetic pregnancy, with ever increasing prevalence, adversely affects embryogenesis and increases vasculometabolic disorder risks in adult offspring. However, it remains poorly understood whether maternal diabetes increases the offspring's susceptibility to heart injuries in adulthood. In this study, we observed that cardiac function and structure were comparable between adult offspring born to diabetic mice and their counterparts born to nondiabetic mice at baseline. However, in response to myocardial ischemia/reperfusion (MIR), diabetic mother offspring exhibited augmented infarct size, cardiac dysfunction, and myocardial apoptosis compared with control, in association with exaggerated activation of mitochondria- and endoplasmic reticulum (ER) stress-mediated apoptosis pathways and oxidative stress. Molecular analysis showed that the impaired myocardial ischemic tolerance in diabetic mother offspring was mainly attributable to blunted cardiac insulin receptor substrate (IRS)-1/Akt signaling. Furthermore, the effect of maternal melatonin administration on offspring's response to MIR was determined, and the results indicated that melatonin treatment in diabetic dams during pregnancy significantly improved the tolerance to MIR injury in their offspring, via restoring cardiac IRS-1/Akt signaling. Taken together, these data suggest that maternal diabetes predisposes offspring to augmented MIR injury in adulthood, and maternal melatonin supplementation during diabetic pregnancy may hold promise for improving myocardial ischemic tolerance in the offspring. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring.

    Science.gov (United States)

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin; Qi, Cuijuan; Wang, Tong

    2015-10-01

    Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32 weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p diet during gestation, lactation and into 32-week age (p diet offspring (p fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.

  16. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

    Science.gov (United States)

    Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-01-01

    Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

  17. Perinatal exposure to perfluorooctane sulfonate affects glucose metabolism in adult offspring.

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    Hin T Wan

    Full Text Available Perfluoroalkyl acids (PFAAs are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0 were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21. To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders.

  18. Adult and offspring size in the ocean over 17 orders of magnitude follows two life history strategies

    DEFF Research Database (Denmark)

    Neuheimer, Anna; Hartvig, Martin; Heuschele, Jan

    2015-01-01

    is observed along with variability in physical and biological forcing factors in space and time. We compiled adult and offspring size for 407 pelagic marine species covering more than 17 orders of magnitude in body mass including Cephalopoda, Cnidaria, Crustaceans, Ctenophora, Elasmobranchii, Mammalia...... discuss where these two strategies occur and how these patterns (along with the relative size of the offspring) may be shaped by physical and biological constraints in the organism’s environment. This adaptive environment along with the evolutionary history of the different groups shape observed life......Explaining variability in offspring vs. adult size among groups is a necessary step to determine the evolutionary and environmental constraints shaping variability in life history strategies. This is of particular interest for life in the ocean where a diversity of offspring development strategies...

  19. Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

    Science.gov (United States)

    Hollander, K S; Tempel Brami, C; Konikoff, F M; Fainaru, M; Leikin-Frenkel, A

    2014-07-01

    Our objective was to test the contribution of dietary enrichment in essential or saturated fatty acids, in normocaloric diets, on the lipid accumulation and insulin resistance in the adult offspring in a C57Bl6/J mice model. Pregnant mothers were fed normocaloric diets containing 6% fat enriched in essential fatty acids (EFA): alpha-linolenic (ALA-18:3, n-3), linoleic (LA-18:2, n-6), or saturated fatty acids (SFA). After a washing-out period with regular diet, the offspring received a high-fat diet before euthanization. Adult mice fed maternal ALA showed lower body weight gain and lower liver fat accumulation, lower HOMA index and lower stearoyl-CoA desaturase (SCD1) activity than those fed maternal SFA. The results observed using this novel model suggest that ALA in maternal diet may have the potential to inhibit insulin resistance in adult offspring.

  20. Maternal High Folic Acid Supplement Promotes Glucose Intolerance and Insulin Resistance in Male Mouse Offspring Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Yifan Huang

    2014-04-01

    Full Text Available Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD. Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control, 5 (recommended folic acid supplement, RFolS or 40 (high folic acid supplement, HFolS mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS were more vulnerable to suffer from obesity (p = 0.009, glucose intolerance (p < 0.001 and insulin resistance (p < 0.001, compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring.

  1. Maternal Grand Multiparity and the Risk of Severe Mental Disorders in Adult Offspring.

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    Marius Lahti

    Full Text Available Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life.Our study sample comprised 13243 Helsinki Birth Cohort Study 1934-1944 participants (6905 men and 6338 women. According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969-2010.Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03, non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002, and suicide attempts (Hazard Ratio = 3.94, p = 0.01 in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01, non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02 schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02, mood disorders (Hazard Ratio = 2.40, p = 0.002, non-psychotic mood disorders (Hazard Ratio = 2.91, p<0.001, and suicide attempts (Hazard Ratio = 5.05, p = 0.01 in adulthood. The effects of maternal grand multiparity on offspring psychopathology risk were independent of maternal age and body mass index at childbirth, and of year of birth, sex, childhood socioeconomic position, and birth weight of the offspring. In contrast, no significant effects were found among men.Women born to grand multiparous mothers are at an increased risk of severe mental disorders and suicide attempts across adulthood. Our findings may inform the

  2. Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring

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    Stephanie A. Segovia

    2018-03-01

    Full Text Available Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl, high-salt (SD; 10% kcal from fat, 4% NaCl, high-fat (HF; 45% kcal from fat, 1% NaCl or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1. There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2. Gut expression of inflammatory (Il1r1, Tnfα, Il6, and Il6r and renin–angiotensin system (Agtr1a, Agtr1b markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin–angiotensin regulation.

  3. Prenatal nicotine exposure induces poor articular cartilage quality in female adult offspring fed a high-fat diet and the intrauterine programming mechanisms.

    Science.gov (United States)

    Tie, Kai; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2016-04-01

    Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mathiesen, Elisabeth R; Hansen, Torben

    2009-01-01

    Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes Context: In animal studies exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms....... Human long-term follow-up studies on the same topic are few. Objective: To study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal...... hyperglycemia and outcome in the offspring Design: Follow-up study of 1,066 primarily Caucasians aged 18-27 years. Setting: Center for pregnant women with diabetes, Rigshospitalet, Denmark Participants: Offspring of women with diet-treated GDM (n=168) and an un-exposed reference group (n=141). Offspring...

  5. Perinatal programming of depressive-like behavior by inflammation in adult offspring mice whose mothers were fed polluted eels: Gender selective effects.

    Science.gov (United States)

    Soualeh, Nidhal; Dridi, Imen; Eppe, Gauthier; Némos, Christophe; Soulimani, Rachid; Bouayed, Jaouad

    2017-07-01

    Several lines of evidence indicate that early-life inflammation may predispose to mental illness, including depression, in later-life. We investigated the impact of perinatal exposure to polluted eels on neonatal, postnatal, and adult brain inflammation, and on the resignation behavior of male and female adult offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Brain inflammatory markers including cytokines were assessed in offspring mice on the day of birth (i.e., on the postnatal day-PND 1), upon weaning (PND 21) and at adulthood (PND 100). Plasma myeloperoxidase and corticosterone levels were evaluated at PND 100. Immobility behavior of offspring was assessed in adulthood (i.e., at PNDs 95-100), using the tail suspension and forced swimming tests. Chronic brain inflammation was found in male and female offspring mice compared to controls, as assessed at PNDs 1, 21, and 100. The level of myeloperoxidase was found to be significantly higher in both adult males and females vs. control offspring. However, high corticosterone levels were only found in male offspring mice that were perinatally exposed to eels, suggesting a gender-selective dysregulation of the adult hypothalamic-pituitaryadrenal (HPA) axis. Gender-specific differences were also detected in adulthood in regard to offspring resignation behavior. Thus, compared to controls, males, but not females, whose mothers were fed eels during pregnancy and lactation exhibited a depressive-like behavior in adult age in both behavioral models of depression. Depressive symptoms were more pronounced in male mice perinatally exposed to either intermediate or highly polluted eels than those exposed to only lowly polluted eels. Our results indicate that early-life inflammatory insult is a plausible causative factor that induces the depressive phenotype exhibited by male adult offspring mice, most likely through a

  6. Maternal high fat diet alters skeletal muscle mitochondrial catalytic activity in adult male rat offspring.

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    Chantal Anne Pileggi

    2016-11-01

    Full Text Available A maternal high-fat (HF diet during pregnancy can lead to metabolic compromise such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat or a high fat diet (HFD; 45% kcal from fat for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1 and mitochondrial transcription factor A (mtTFA were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS respiratory complex subunits were supressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%, which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%. Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle.

  7. Levels of maternal care in dogs affect adult offspring temperament.

    Science.gov (United States)

    Foyer, Pernilla; Wilsson, Erik; Jensen, Per

    2016-01-13

    Dog puppies are born in a state of large neural immaturity; therefore, the nervous system is sensitive to environmental influences early in life. In primates and rodents, early experiences, such as maternal care, have been shown to have profound and lasting effects on the later behaviour and physiology of offspring. We hypothesised that this would also be the case for dogs with important implications for the breeding of working dogs. In the present study, variation in the mother-offspring interactions of German Shepherd dogs within the Swedish breeding program for military working dogs was studied by video recording 22 mothers with their litters during the first three weeks postpartum. The aim was to classify mothers with respect to their level of maternal care and to investigate the effect of this care on pup behaviour in a standardised temperament test carried out at approximately 18 months of age. The results show that females differed consistently in their level of maternal care, which significantly affected the adult behaviour of the offspring, mainly with respect to behaviours classified as Physical and Social Engagement, as well as Aggression. Taking maternal quality into account in breeding programs may therefore improve the process of selecting working dogs.

  8. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    International Nuclear Information System (INIS)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-01-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT 2 R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT 1a R)/AT 2 R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT 2 R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT 2 R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits

  9. Complex life cycles and offspring provisioning in marine invertebrates.

    Science.gov (United States)

    Marshall, Dustin J; Keough, Michael J

    2006-10-01

    Offspring size can have pervasive effects throughout an organism's life history. Mothers can make either a few large or many small offspring, and the balance between these extremes is determined by the relationship between offspring size and performance. This relationship in turn is thought to be determined by the offspring's environment. Recently, it has become clear that events in one life-history stage can strongly affect performance in another. Given these strong carryover effects, we asked whether events in the larval phase can change the relationship between offspring size and performance in the adult phase. We manipulated the length of the larval period in the bryozoan Bugula neritina and then examined the relationship between offspring size and various parameters of adult performance under field conditions. We found that despite the adult stage being outplanted into identical conditions, different offspring sizes were predicted to be optimal, depending on the experience of those adults as larvae. This work highlights the fact that the strong phenotypic links between life-history stages may result in optimal offspring size being highly unpredictable for organisms with complex life cycles.

  10. Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation.

    Science.gov (United States)

    Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

    2018-03-01

    Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as

  11. Prenatal exposure to dexamethasone in the mouse alters cardiac growth patterns and increases pulse pressure in aged male offspring.

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    Lee O'Sullivan

    Full Text Available Exposure to synthetic glucocorticoids during development can result in later cardiovascular and renal disease in sheep and rats. Although prenatal glucocorticoid exposure is associated with impaired renal development, less is known about effects on the developing heart. This study aimed to examine the effects of a short-term exposure to dexamethasone (60 hours from embryonic day 12.5 on the developing mouse heart, and cardiovascular function in adult male offspring. Dexamethasone (DEX exposed fetuses were growth restricted compared to saline treated controls (SAL at E14.5, but there was no difference between groups at E17.5. Heart weights of the DEX fetuses also tended to be smaller at E14.5, but not different at E17.5. Cardiac AT1aR, Bax, and IGF-1 mRNA expression was significantly increased by DEX compared to SAL at E17.5. In 12-month-old offspring DEX exposure caused an increase in basal blood pressure of ~3 mmHg. In addition, DEX exposed mice had a widened pulse pressure compared to SAL. DEX exposed males at 12 months had an approximate 25% reduction in nephron number compared to SAL, but no difference in cardiomyocyte number. Exposure to DEX in utero appears to adversely impact on nephrogenesis and heart growth but is not associated with a cardiomyocyte deficit in male mice in adulthood, possibly due to compensatory growth of the myocardium following the initial insult. However, the widened pulse pressure may be indicative of altered vascular compliance.

  12. Aberrant Epigenetic Gene Regulation in GABAergic Interneuron Subpopulations in the Hippocampal Dentate Gyrus of Mouse Offspring Following Developmental Exposure to Hexachlorophene.

    Science.gov (United States)

    Watanabe, Yousuke; Abe, Hajime; Nakajima, Kota; Ideta-Otsuka, Maky; Igarashi, Katsuhide; Woo, Gye-Hyeong; Yoshida, Toshinori; Shibutani, Makoto

    2018-05-01

    Maternal hexachlorophene (HCP) exposure causes transient disruption of hippocampal neurogenesis in mouse offspring. We examined epigenetically hypermethylated and downregulated genes related to this HCP-induced disrupted neurogenesis. Mated female mice were dietary exposed to 0 or 100 ppm HCP from gestational day 6 to postnatal day (PND) 21 on weaning. The hippocampal dentate gyrus of male offspring was subjected to methyl-capture sequencing and real-time reverse transcription-polymerase chain reaction analyses on PND 21. Validation analyses on methylation identified three genes, Dlx4, Dmrt1, and Plcb4, showing promoter-region hypermethylation. Immunohistochemically, DLX4+, DMRT1+, and PLCB4+ cells in the dentate hilus co-expressed GAD67, a γ-aminobutyric acid (GABA)ergic neuron marker. HCP decreased all of three subpopulations as well as GAD67+ cells on PND 21. PLCB4+ cells also co-expressed the metabotropic glutamate receptor, GRM1. HCP also decreased transcript level of synaptic plasticity-related genes in the dentate gyrus and immunoreactive granule cells for synaptic plasticity-related ARC. On PND 77, all immunohistochemical cellular density changes were reversed, whereas the transcript expression of the synaptic plasticity-related genes fluctuated. Thus, HCP-exposed offspring transiently reduced the number of GABAergic interneurons. Among them, subpopulations expressing DLX4, DMRT1, or PLCB4 were transiently reduced in number through an epigenetic mechanism. Considering the role of the Dlx gene family in GABAergic interneuron migration and differentiation, the decreased number of DLX4+ cells may be responsible for reducing those GABAergic interneurons regulating neurogenesis. The effect on granule cell synaptic plasticity was sustained until the adult stage, and reduced GABAergic interneurons active in GRM1-PLCB4 signaling may be responsible for the suppression on weaning.

  13. Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

    Science.gov (United States)

    Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

    2014-01-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

  14. Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring.

    Science.gov (United States)

    Kiryanova, V; Meunier, S J; Vecchiarelli, H A; Hill, M N; Dyck, R H

    2016-04-21

    Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults. C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non-stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress (PS), perinatal Flx, PS and Flx, or neither PS or Flx, went through a comprehensive behavioral test battery. At the end of testing brain-derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring. Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive

  15. Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring

    Directory of Open Access Journals (Sweden)

    Masato Tanaka

    2017-03-01

    Full Text Available Resveratrol (3,5,4-trihydroxystilbene is a natural polyphenolic compound found in grapes and red wine and has been shown to exert protective effects on the liver preventing lipid accumulation induced by a high-fat diet. However, no studies have shown that the nutritional resveratrol intake by the parental generation has modified lipogenesis in an adult offspring. The aim of this study was to investigate whether maternal resveratrol intake during lactation affects lipogenesis in adult male rat offspring, and if it does, what is the molecular mechanistic basis. Six male pups born from mothers given a control diets during lactation (CC group and six male pups born from mothers given a control diet as well as resveratrol during lactation (CR group were fed a standard diet until sacrifice at 36 weeks. Adult male offspring from mothers given resveratrol during lactation (CR group had lower body weight from the fourth week of lactation until adulthood, but no significant change was observed in the relative food intake. Low levels of plasma triacylglycerol were found in the CR group compared to the CC group. Histopathological analysis of the livers of adult male rat offspring revealed lipid accumulation in hepatocytes in the CC group, whereas lipid droplets were rare in the CR group. Hepatic protein levels of AMPK-phosphorylated at ser403, Sirt1, and Nampt in the CR group were upregulated significantly compared to the CC group. These results indicated the maternal resveratrol intake during lactation-induced activation of AMPK through Sirt1 upregulation. In this study, significant upregulation of the levels of precursor of sterol regulatory element binding protein-1c (SREBP-1c and downregulation of the ratio of active-SREBP-1c/precusor-SREBP-1c were observed in the CR group compared to the CC group. These results suggested that proteolytic processing of SREBP-1c was suppressed by AMPK in the livers of the CR group. It is well known that SREBP-1c

  16. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    Science.gov (United States)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. Copyright © 2015. Published by Elsevier Inc.

  17. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ao, Ying [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China); Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Li, Bin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Yang, Shuailong; Xia, Liping; Wu, Yong [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); He, Zheng [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  18. Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring.

    Science.gov (United States)

    Lee, Kuan-I; Chiang, Chin-Wei; Lin, Hui-Ching; Zhao, Jin-Feng; Li, Cheng-Ta; Shyue, Song-Kun; Lee, Tzong-Shyuan

    2016-05-01

    Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring.

  19. Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

    Science.gov (United States)

    Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

    2012-12-17

    Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

  20. Purification of oogonial stem cells from adult mouse and human ovaries: an assessment of the literature and a view toward the future.

    Science.gov (United States)

    Woods, Dori C; White, Yvonne A R; Tilly, Jonathan L

    2013-01-01

    Contemporary claims that mitotically active female germ line or oogonial stem cells (OSCs) exist and support oogenesis during postnatal life in mammals have been debated in the field of reproductive biology since March 2004, when a mouse study posed the first serious challenge to the dogma of a fixed pool of oocytes being endowed at birth in more than 50 years. Other studies have since been put forth that further question the validity of this dogma, including the isolation of OSCs from neonatal and adult mouse ovaries by 4 independent groups using multiple strategies. Two of these groups also reported that isolated mouse OSCs, once transplanted back into ovaries of adult female mice, differentiate into fully functional eggs that ovulate, fertilize, and produce healthy embryos and offspring. Arguably, one of the most significant advances in this emerging field was provided by a new research study published this year, which reported the successful isolation and functional characterization of OSCs from ovaries of reproductive age women. Two commentaries on this latest work, one cautiously supportive and one highly skeptical, were published soon afterward. This article evaluates the current literature regarding postnatal oogenesis in mammals and discusses important next steps for future work on OSC biology and function.

  1. Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

    Directory of Open Access Journals (Sweden)

    Michele La Merrill

    Full Text Available Dichlorodiphenyltrichloroethane (DDT has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

  2. Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

    Science.gov (United States)

    La Merrill, Michele; Karey, Emma; Moshier, Erin; Lindtner, Claudia; La Frano, Michael R.; Newman, John W.; Buettner, Christoph

    2014-01-01

    Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring. PMID:25076055

  3. Parental Midlife Body Shape and Association with Multiple Adult Offspring Obesity Measures: North West Adelaide Health Study.

    Directory of Open Access Journals (Sweden)

    Janet F Grant

    Full Text Available There is compelling evidence that parental weight is a strong determinant of offspring weight status. The study used cross-sectional self-reported and measured data from a longitudinal cohort of Australian adults (n = 2128 from Stage 3 (2008-10 of the North West Adelaide Health Study (1999-2003, baseline n = 4056 to investigate the association between midlife parental body shape and four indicators of obesity and fat distribution. The analysis used measured body mass index (BMI, waist circumference (WC, waist hip ratio (WHR and waist height ratio (WHtR of adult offspring, together with pictograms for recall of parental body shape. Compared to both parents being a healthy weight, offspring were more likely to be overweight or obese if both parents were an unhealthy weight at age 40 (OR 2.14, 95% CI 1.67-2.76 and further, those participants whose mother was an unhealthy weight were more likely to be overweight or obese themselves (OR 1.50, 95% CI 1.14-1.98. There were similar but lower results for those with an overweight/obese father (OR 1.44, 95% CI 1.08-1.93. The effect of one or both parents being overweight or obese tended to be stronger for daughters than for sons across BMI, WC and WHtR. BMI showed the strongest association with parental body shape (OR 2.14, followed by WC (OR 1.78, WHtR (OR 1.71 and WHR (OR 1.45. WHtR (42-45% and BMI (35-36% provided the highest positive predictive values for overweight/obesity from parental body shape. Parental obesity increases the risk of obesity for adult offspring, both for overall body shape and central adiposity, particularly for daughters. Pictograms could potentially be used as a screening tool in primary care settings to promote healthy weight among young adults.

  4. Parental history of moderate to severe infantile malnutrition is associated with cognitive deficits in their adult offspring.

    Science.gov (United States)

    Waber, Deborah P; Bryce, Cyralene P; Girard, Jonathan M; Fischer, Laura K; Fitzmaurice, Garrett M; Galler, Janina R

    2018-04-01

    We compared the IQ and academic achievement of the young adult offspring of parents malnourished in infancy and those of a healthy control group in order to test the hypothesis that the offspring of previously malnourished individuals would show IQ and academic deficits that could be related to reduced parental socioeconomic status. We conducted a group comparison study based on a community sample in Barbados (Barbados Nutrition Study). Participants were adult children ≥16 years of age whose parents had been malnourished during the first year of life (n = 64; Mean age 19.3 years; 42% male) or whose parents were healthy community controls (n = 50; Mean age 19.7 years; 48% male). The primary outcome was estimated IQ (Wechsler Abbreviated Scale of Intelligence); a secondary outcome was academic achievement (Wide Range Achievement Test - Third Edition). Data were analyzed using PROC MIXED with and without adjusting for parental socioeconomic status (Hollingshead Index of Social Position). IQ was reduced in the offspring of previously malnourished parents relative to the offspring of controls (9.8 point deficit; P malnutrition on cognitive function may be transmitted to the next generation; however, this intergenerational effect does not appear to be explained by the reduced socioeconomic status or IQ of the parent generation.

  5. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    International Nuclear Information System (INIS)

    Wang, Lingxing; Cai, Ruowei; Lv, Guorong; Huang, Ziyang; Wang, Zhenhua

    2010-01-01

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  6. Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring - a mouse study.

    Science.gov (United States)

    Venerosi, Aldina; Tait, Sabrina; Stecca, Laura; Chiarotti, Flavia; De Felice, Alessia; Cometa, Maria Francesca; Volpe, Maria Teresa; Calamandrei, Gemma; Ricceri, Laura

    2015-04-02

    Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides worldwide. Epidemiological studies on pregnant women and their children suggest a link between in utero CPF exposure and delay in psychomotor and cognitive maturation. A large number of studies in animal models have shown adverse effects of CPF on developing brain and more recently on endocrine targets. Our aim was to determine if developmental exposure to CPF affects social responsiveness and associated molecular neuroendocrine markers at adulthood. Pregnant CD1 outbred mice were fed from gestational day 15 to lactation day 14 with either a CPF-added (equivalent to 6 mg/kg/bw/day during pregnancy) or a standard diet. We then assessed in the offspring the long-term effects of CPF exposure on locomotion, social recognition performances and gene expression levels of selected neurondocrine markers in amygdala and hypothalamus. No sign of CPF systemic toxicity was detected. CPF induced behavioral alterations in adult offspring of both sexes: CPF-exposed males displayed enhanced investigative response to unfamiliar social stimuli, whereas CPF-exposed females showed a delayed onset of social investigation and lack of reaction to social novelty. In parallel, molecular effects of CPF were sex dimorphic: in males CPF increased expression of estrogen receptor beta in hypothalamus and decreased oxytocin expression in amygdala; CPF increased vasopressin 1a receptor expression in amygdala in both sexes. These data indicate that developmental CPF affects mouse social behavior and interferes with development of sex-dimorphic neuroendocrine pathways with potential disruptive effects on neuroendocrine axes homeostasis. The route of exposure selected in our study corresponds to relevant human exposure scenarios, our data thus supports the view that neuroendocrine effects, especially in susceptible time windows, should deserve more attention in risk assessment of OP insecticides.

  7. Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

    Science.gov (United States)

    Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

    2016-04-01

    Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring.

    Science.gov (United States)

    Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A

    2016-04-01

    A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model.

    Directory of Open Access Journals (Sweden)

    Heather A Enright

    Full Text Available Triclocarban (TCC is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS. 14C-TCC (100 nM was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

  10. Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model.

    Science.gov (United States)

    Enright, Heather A; Falso, Miranda J S; Malfatti, Michael A; Lao, Victoria; Kuhn, Edward A; Hum, Nicholas; Shi, Yilan; Sales, Ana Paula; Haack, Kurt W; Kulp, Kristen S; Buchholz, Bruce A; Loots, Gabriela G; Bench, Graham; Turteltaub, Kenneth W

    2017-01-01

    Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

  11. Maternal high-fat diet associated with altered gene expression, DNA methylation, and obesity risk in mouse offspring

    Science.gov (United States)

    Zaidi, Rabab; Shah, Shyam; Oakley, M. Elsa; Pavlatos, Cassondra; El Idrissi, Samir; Xing, Xiaoyun; Li, Daofeng; Wang, Ting; Cheverud, James M.

    2018-01-01

    We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes. PMID:29447215

  12. Maternal high-fat diet associated with altered gene expression, DNA methylation, and obesity risk in mouse offspring.

    Science.gov (United States)

    Keleher, Madeline Rose; Zaidi, Rabab; Shah, Shyam; Oakley, M Elsa; Pavlatos, Cassondra; El Idrissi, Samir; Xing, Xiaoyun; Li, Daofeng; Wang, Ting; Cheverud, James M

    2018-01-01

    We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes.

  13. New Insights on the Morphology of Adult Mouse Penis1

    Science.gov (United States)

    Rodriguez, Esequiel; Weiss, Dana A.; Yang, Jennifer H.; Menshenina, Julia; Ferretti, Max; Cunha, Tristan J.; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Cunha, Gerald R.; Baskin, Laurence S.

    2011-01-01

    ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development. PMID:21918128

  14. Methyl donor supplementation blocks the adverse effects of maternal high fat diet on offspring physiology.

    Directory of Open Access Journals (Sweden)

    Jesselea Carlin

    Full Text Available Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60% diet leads to global and gene specific decreases in DNA methylation in the brain of the offspring. The present experiments were designed to attempt to reverse this DNA hypomethylation through supplementation of the maternal diet with methyl donors, and to determine whether methyl donor supplementation could block or attenuate phenotypes associated with maternal consumption of a HF diet. Metabolic and behavioral (fat preference outcomes were assessed in male and female adult offspring. Expression of the mu-opioid receptor and dopamine transporter mRNA, as well as global DNA methylation were measured in the brain. Supplementation of the maternal diet with methyl donors attenuated the development of some of the adverse effects seen in offspring from dams fed a high fat diet; including weight gain, increased fat preference (males, changes in CNS gene expression and global hypomethylation in the prefrontal cortex. Notable sex differences were observed. These findings identify the importance of balanced methylation status during pregnancy, particularly in the context of a maternal high fat diet, for optimal offspring outcome.

  15. ATM localization and gene expression in the adult mouse eye.

    Science.gov (United States)

    Leemput, Julia; Masson, Christel; Bigot, Karine; Errachid, Abdelmounaim; Dansault, Anouk; Provost, Alexandra; Gadin, Stéphanie; Aoufouchi, Said; Menasche, Maurice; Abitbol, Marc

    2009-01-01

    High levels of metabolism and oxygen consumption in most adult murine ocular compartments, combined with exposure to light and ultraviolet (UV) radiation, are major sources of oxidative stress, causing DNA damage in ocular cells. Of all mammalian body cells, photoreceptor cells consume the largest amount of oxygen and generate the highest levels of oxidative damage. The accumulation of such damage throughout life is a major factor of aging tissues. Several multiprotein complexes have recently been identified as the major sensors and mediators involved in the maintenance of DNA integrity. The activity of these complexes initially seemed to be restricted to dividing cells, given their ultimate role in major cell cycle checkpoints. However, it was later established that they are also active in post-mitotic cells. Recent findings demonstrate that the DNA damage response (DDR) is essential for the development, maintenance, and normal functioning of the adult central nervous system. One major molecular factor in the DDR is the protein, ataxia telangiectasia mutated (ATM). It is required for the rapid induction of cellular responses to DNA double-strand breaks. These cytotoxic DNA lesions may be caused by oxidative damage. To understand how ATM prevents oxidative stress and participates in the maintenance of genomic integrity and cell viability of the adult retina, we determined the ATM expression patterns and studied its localization in the adult mouse eye. Atm gene expression was analyzed by RT-PCR experiments and its localization by in situ hybridization on adult mouse ocular and cerebellar tissue sections. ATM protein expression was determined by western blot analysis of proteins homogenates extracted from several mouse tissues and its localization by immunohistochemistry experiments performed on adult mouse ocular and cerebellar tissue sections. In addition, subcellular localization was realized by confocal microscopy imaging of ocular tissue sections, with a special

  16. Inducing maternal inflammation promotes leptin production in offspring but does not improve allergic symptoms in a mouse model of allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Atsuko Imai

    2017-06-01

    Full Text Available Aims: The intrauterine environment is considered to affect immunological development in fetus, leading to an increased risk of developing allergy. In particular, maternal lipopolysaccharides (LPS administration might regulate the development of allergic disease in offspring. Several studies have shown that being obese relates to a higher prevalence of allergic diseases compared to normal weight. The present study explored the effects of inducing maternal inflammation with LPS before pregnancy on body weight, physical composition including body fat, adipokine production, and pathology of allergic rhinitis in offspring. Main methods: Female mice received a single intraperitoneal injection of LPS (2 μg/g BW. After 5 days of LPS administration, female mice were mated with males, and experimental allergic rhinitis was induced in female offspring. Immunization and nasal challenge with ovalbumin (OVA were performed at 7 and 8 weeks of age. Allergic rhinitis-like symptoms, OVA-specific IgE and adipokines in sera, body weight, fat pad weight, and cytokine production by splenocytes in these 9-week-old offspring. Key findings: Maternal LPS administration results in a significant increase in body weight, visceral fat accumulation, and serum leptin concentration, and the dominance of Th1 in Th balance. Nevertheless, there was no statistical difference in OVA-specific IgE titer and allergic-like symptoms between the groups. Significance: In conclusion, maternal LPS promoted leptin production and altered Th balance in mice offspring, but not improved allergic symptoms in a mouse model of allergic rhinitis. It might suggest that inflammation during pregnancy plays a role in the adipose tissue function which could diversely influence allergic inflammation in offspring. Keywords: Immunology, Metabolism, Nutrition, Health Sciences

  17. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    Science.gov (United States)

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR. © FASEB.

  18. A Comprehensive Atlas of the Adult Mouse Penis

    Science.gov (United States)

    Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.

    2016-01-01

    Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156

  19. The influence of parental history of diabetes and offspring birthweight on offspring glucose metabolism in adulthood

    DEFF Research Database (Denmark)

    Lauenborg, Jeannet; Jørgensen, Mie Kw; Damm, Peter

    2011-01-01

    Background. Links are well established between both family history of diabetes and reduced birthweight and increased risk of diabetes in adulthood. Objectives. 1) To investigate the influence of parental history of type 2 diabetes (T2DM) on offspring birthweight and adult offspring glucose tolera...

  20. Effects and Interactions of Prenatal Ethanol Exposure, a Post-Weaning High-Fat Diet and Gender on Adult Hypercholesterolemia Occurrence in Offspring Rats.

    Science.gov (United States)

    Qi, Yongjian; Luo, Hanwen; Hu, Shuwei; Wu, Yimeng; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2017-01-01

    Prenatal ethanol exposure (PEE) could induce intrauterine programming of hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolism, resulting in intrauterine growth retardation and susceptibility to adult hypercholesterolemia in offspring. This study aimed to analyse the effects and interactions of PEE, a post-weaning high-fat diet (HFD) and gender on the occurrence of adult hypercholesterolemia in offspring rats. Wistar female rats were treated with ethanol (4 g/kg.d) at gestational days 11-20. The offspring were given a normal diet or HFD after weaning, and the blood cholesterol metabolism phenotype and expression of hepatic cholesterol metabolism related genes were detected in 24-week-old offspring. Furthermore, the interactions among PEE, HFD, and gender on hypercholesterolemia occurrence were analysed. PEE increased the serum total cholesterol (TCH) and low-density lipoprotein-cholesterol (LDL-C) levels and decreased the serum high-density lipoprotein-cholesterol (HDL-C) level in adult offspring rats; the changes in female offspring were greater than those in males. At the same time, the mRNA expression levels of hepatic cholesterol metabolic enzymes (apolipoprotein B (ApoB) and 7α-hydroxylase (CYP7A1))-were increased, while the mRNA expression levels of the scavenger receptor B1 (SR-B1) and LDL receptor (LDLR) were decreased. Furthermore, a three-way ANOVA showed there were interactions among PEE, post-weaning HFD and gender. For PEE offspring, a post-weaning HFD aggravated the elevated hepatic ApoB and CYP7A1 expression and reduced SR-B1 and LDLR expression; the changes in hepatic SR-B1 and CYP7A1 expression were greater in female HFD rats than in males. Our findings suggest that a post-weaning HFD could aggravate offspring hypercholesterolemia caused by PEE and that this mechanism might be associated with hepatic cholesterol metabolic disorders that are aggravated by a post-weaning HFD; hepatic cholesterol metabolism was more sensitive to

  1. Intergenerational Transmission of Resilience? Sense of Coherence Is Associated between Lithuanian Survivors of Political Violence and Their Adult Offspring.

    Science.gov (United States)

    Kazlauskas, Evaldas; Gailiene, Danute; Vaskeliene, Ieva; Skeryte-Kazlauskiene, Monika

    2017-01-01

    Little is known about intergeneration effects on mental health in the families of survivors of political oppression of communist regime in Central and Eastern Europe. We aimed to explore post-traumatic stress in the second generation of the Lithuanian survivors of political violence, and analyze links between parental and adult offsprings' sense of coherence in the families exposed to political violence during the oppressive communist regime in Lithuania. A total of 110 matched pairs of communist regime political violence survivors (mean age = 73.22 years) and their adult offspring (mean age = 44.65 years) participated in this study. Life-time traumatic experiences and sense of coherence were measured in both parents and their offspring. Post-traumatic stress symptoms were assessed in the second generation of survivors. We found a high vulnerability in the second generation of the Lithuanian families of political violence survivors, with a 29% of probable PTSD in the second generation based on self-report measures. A significant positive correlation between parental and adult offsprings' sense of coherence was found. Post-traumatic stress symptoms were associated negatively with a sense of coherence in the second generation. Our study indicates the links between parental and the second generation's sense of coherence in the families of survivors of political violence. The study raises broader questions about the intergenerational aspects of resilience. Further studies are needed to explore the links between parental and child sense of coherence in other samples.

  2. Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

    Science.gov (United States)

    Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

    2017-05-01

    Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O 3 ). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O 3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O 3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O 3 . Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O 3 with responses markedly exacerbated in males. HF diet and O 3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O 3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O 3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O 3 in their adult offspring in a sex-specific manner.

  3. Glutamate neurotransmission is affected in prenatally stressed offspring

    DEFF Research Database (Denmark)

    Adrover, Ezequiela; Pallarés, Maria Eugenia; Baier, Carlos Javier

    2015-01-01

    Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization with syn......Previous studies from our laboratory have shown that male adult offspring of stressed mothers exhibited higher levels of ionotropic and metabotropic glutamate receptors than control rats. These offspring also showed long-lasting astroglial hypertrophy and a reduced dendritic arborization...... with synaptic loss. Since metabolism of glutamate is dependent on interactions between neurons and surrounding astroglia, our results suggest that glutamate neurotransmitter pathways might be impaired in the brain of prenatally stressed rats. To study the effect of prenatal stress on the metabolism...... was not affected it was found that prenatal stress (PS) changed the expression of the transporters, thus, producing a higher level of vesicular vGluT-1 in the frontal cortex (FCx) and elevated levels of GLT1 protein and messenger RNA in the hippocampus (HPC) of adult male PS offspring. We also observed increased...

  4. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

    NARCIS (Netherlands)

    Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

    AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

  5. Affinity to host population stimulates physical growth in adult offspring of Turkish migrants in Germany.

    Science.gov (United States)

    Özer, Aydan; Scheffler, Christiane

    2018-01-18

    Because of political conflicts and climate change, migration will be increased worldwide and integration in host societies is a challenge also for migrants. We hypothesize that migrants, who take up the challenge in a new social environment are taller than migrants who do not pose this challenge. We analyze by a questionnaire possible social, nutritional and ethnic influencing factors to body height (BH) of adult offspring of Turkish migrants (n = 82, 39 males) aged from 18 to 34 years (mean age 24.6 years). The results of multiple regression (downward selection) show that the more a male adult offspring of Turkish migrants feels like belonging to the Turkish culture, the smaller he is (95% CI, -3.79, -0.323). Further, the more a male adult offspring of Turkish migrants feels like belonging to the German culture, the taller he is (95% CI, -0.152, 1.738). We discussed it comparable to primates taking up their challenge in dominance, where as a result their body size increase is associated with higher IGF-1 level. IGF-1 is associated with emotional belonging and has a fundamental role in the regulation of metabolism and growth of the human body. With all pilot characteristics of our study results show that the successful challenge of integration in a new society is strongly associated with the emotional integration and identification in the sense of a personal sense of belonging to society. We discuss taller BH as a signal of social growth adjustment. In this sense, a secular trend of BH adaptation of migrants to hosts is a sign of integration.

  6. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    International Nuclear Information System (INIS)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-01

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  7. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  8. Educational Attainments of Immigrant Offspring: Success or Segmented Assimilation?

    Science.gov (United States)

    Boyd, Monica

    2002-01-01

    Examined the educational attainments of adult offspring of immigrants age 20-64 years, analyzing data from Canada's 1996 Survey of Labour and Income Dynamics. Contrary to second generation decline and segmented underclass assimilation found in the United States, Canadian adult visible-minority immigrant offspring did not have lower educational…

  9. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Directory of Open Access Journals (Sweden)

    Olena Rudyk

    Full Text Available Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11 or lard-enriched (23.6% fat, n = 16 chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old offspring cardiovascular parameters were measured (radiotelemetry. The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF and controls (OC. However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP and Δheart rate (HR with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week male OF demonstrated higher SBP (p<0.05 in the awake phase (night-time and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  10. Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

    International Nuclear Information System (INIS)

    Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui

    2014-01-01

    Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1 + or nestin + stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU + cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU + cells, very few are mash1 + or nestin + stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1 + microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

  11. Pre-weaning growth hormone treatment reverses hypertension and endothelial dysfunction in adult male offspring of mothers undernourished during pregnancy.

    Directory of Open Access Journals (Sweden)

    Clint Gray

    Full Text Available Maternal undernutrition results in elevated blood pressure (BP and endothelial dysfunction in adult offspring. However, few studies have investigated interventions during early life to ameliorate the programming of hypertension and vascular disorders. We have utilised a model of maternal undernutrition to examine the effects of pre-weaning growth hormone (GH treatment on BP and vascular function in adulthood. Female Sprague-Dawley rats were fed either a standard control diet (CON or 50% of CON intake throughout pregnancy (UN. From neonatal day 3 until weaning (day 21, CON and UN pups received either saline (CON-S, UN-S or GH (2.5 ug/g/day(CON-GH, UN-GH. All dams were fed ad libitum throughout lactation. Male offspring were fed a standard diet until the end of the study. Systolic blood pressure (SBP was measured at day 150 by tail cuff plethysmography. At day 160, intact mesenteric vessels mounted on a pressure myograph. Responses to pressure, agonist-induced constriction and endothelium-dependent vasodilators were investigated to determine vascular function. SBP was increased in UN-S groups and normalised in UN-GH groups (CON-S 121±2 mmHg, CON-GH 115±3, UN-S 146±3, UN-GH 127±2. Pressure mediated dilation was reduced in UN-S offspring and normalised in UN-GH groups. Vessels from UN-S offspring demonstrated a reduced constrictor response to phenylephrine and reduced vasodilator response to acetylcholine (ACh. Furthermore, UN-S offspring vessels displayed a reduced vasodilator response in the presence of L-NG-Nitroarginine Methyl Ester (L-NAME, carbenoxolone (CBX, L-NAME and CBX, Tram-34 and Apamin. UN-GH vessels showed little difference in responses when compared to CON and significantly increased vasodilator responses when compared to UN-S offspring. Pre-weaning GH treatment reverses the negative effects of maternal UN on SBP and vasomotor function in adult offspring. These data suggest that developmental cardiovascular programming is

  12. Impact of maternal melatonin suppression on forced swim and tail suspension behavioral despair tests in adult offspring.

    Science.gov (United States)

    Voiculescu, S E; Rosca, A E; Zeca, V; Zagrean, L; Zagrean, A M

    2015-01-01

    Melatonin is an essential hormone, which regulates circadian rhythms and has antioxidative and anticarcinogenic effects. As melatonin secretion is suppressed by light, this effect was examined on the offspring of the Wistar rat females exposed to continuous light (500 lux) during the second half of the pregnancy (day 12 to 21). Control rats were kept under a 12:12 light-dark cycle. The resulted male offspring have been behaviorally assessed for depression after postnatal day 60 by using Forced Swim Test (FST) and Tail Suspension Test (TST). Animals resulted from the melatonin deprived pregnancies have developed an abnormal response in the TST, but a normal FST behavior. Also, TST active movement was different in the melatonin suppression group compared to the control group. These findings suggest that intrauterine melatonin deprivation might be linked to the depressive like behavior in adult male offspring.

  13. Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring.

    Directory of Open Access Journals (Sweden)

    Julia A Sabet

    Full Text Available The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Male Apc1638N mice (prone to intestinal tumor formation were fed diets containing replete (control, CTRL, mildly deficient (DEF, or supplemental (SUPP quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.In this animal model, modulation of paternal B vitamin intake prior to mating

  14. Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

    Directory of Open Access Journals (Sweden)

    George Panagis

    2017-04-01

    Full Text Available Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ9-tetrahydrocannabinol (Δ9-THC induces transgenerational effects on the reward-facilitating effects of Δ9-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ9-THC (0.1 or 1 mg/kg, i.p. or vehicle during postnatal days 28–50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ9-THC’s (0, 0.1, 0.5, and 1 mg/kg, i.p. and d-amphetamine’s (0, 0.1, 0.5, and 1 mg/kg, i.p. reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ9-THC was abolished in the F1 offspring of females that were exposed to Δ9-THC (0.1 or 1 mg/kg, whereas the reward-attenuating effect of the 1 mg dose of Δ9-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ9-THC (1 mg/kg and 0.1 or 1 mg, respectively. The present results reveal that female Δ9-THC exposure during adolescence can diminish the reward-facilitating effects of Δ9-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ9-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

  15. Female partner preferences enhance offspring ability to survive an infection.

    Science.gov (United States)

    Raveh, Shirley; Sutalo, Sanja; Thonhauser, Kerstin E; Thoß, Michaela; Hettyey, Attila; Winkelser, Friederike; Penn, Dustin J

    2014-01-23

    It is often suggested that mate choice enhances offspring immune resistance to infectious diseases. To test this hypothesis, we conducted a study with wild-derived house mice (Mus musculus musculus) in which females were experimentally mated either with their preferred or non-preferred male, and their offspring were infected with a mouse pathogen, Salmonella enterica (serovar Typhimurium). We found that offspring sired by preferred males were significantly more likely to survive the experimental infection compared to those sired by non-preferred males. We found no significant differences in the pathogen clearance or infection dynamics between the infected mice, suggesting that offspring from preferred males were better able to cope with infection and had improved tolerance rather than immune resistance. Our results provide the first direct experimental evidence within a single study that partner preferences enhance offspring resistance to infectious diseases.

  16. Porcine induced pluripotent stem cells produce chimeric offspring.

    Science.gov (United States)

    West, Franklin D; Terlouw, Steve L; Kwon, Dae Jin; Mumaw, Jennifer L; Dhara, Sujoy K; Hasneen, Kowser; Dobrinsky, John R; Stice, Steven L

    2010-08-01

    Ethical and moral issues rule out the use of human induced pluripotent stem cells (iPSCs) in chimera studies that would determine the full extent of their reprogrammed state, instead relying on less rigorous assays such as teratoma formation and differentiated cell types. To date, only mouse iPSC lines are known to be truly pluripotent. However, initial mouse iPSC lines failed to form chimeric offspring, but did generate teratomas and differentiated embryoid bodies, and thus these specific iPSC lines were not completely reprogrammed or truly pluripotent. Therefore, there is a need to address whether the reprogramming factors and process used eventually to generate chimeric mice are universal and sufficient to generate reprogrammed iPSC that contribute to chimeric offspring in additional species. Here we show that porcine mesenchymal stem cells transduced with 6 human reprogramming factors (POU5F1, SOX2, NANOG, KLF4, LIN28, and C-MYC) injected into preimplantation-stage embryos contributed to multiple tissue types spanning all 3 germ layers in 8 of 10 fetuses. The chimerism rate was high, 85.3% or 29 of 34 live offspring were chimeras based on skin and tail biopsies harvested from 2- to 5-day-old pigs. The creation of pluripotent porcine iPSCs capable of generating chimeric offspring introduces numerous opportunities to study the facets significantly affecting cell therapies, genetic engineering, and other aspects of stem cell and developmental biology.

  17. Older maternal age is associated with depression, anxiety, and stress symptoms in young adult female offspring.

    Science.gov (United States)

    Tearne, Jessica E; Robinson, Monique; Jacoby, Peter; Allen, Karina L; Cunningham, Nadia K; Li, Jianghong; McLean, Neil J

    2016-01-01

    The evidence regarding older parental age and incidence of mood disorder symptoms in offspring is limited, and that which exists is mixed. We sought to clarify these relationships by using data from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study provided comprehensive data from 2,900 pregnancies, resulting in 2,868 live born children. A total of 1,220 participants completed the short form of the Depression Anxiety Stress Scale (DASS-21) at the 20-year cohort follow-up. We used negative binomial regression analyses with log link and with adjustment for known perinatal risk factors to examine the extent to which maternal and paternal age at childbirth predicted continuous DASS-21 index scores. In the final multivariate models, a maternal age of 30-34 years was associated with significant increases in stress DASS-21 scores in female offspring relative to female offspring of 25- to 29-year-old mothers. A maternal age of 35 years and over was associated with increased scores on all DASS-21 scales in female offspring. Our results indicate that older maternal age is associated with depression, anxiety, and stress symptoms in young adult females. Further research into the mechanisms underpinning this relationship is needed. (c) 2016 APA, all rights reserved.

  18. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    Science.gov (United States)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  19. Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection.

    Science.gov (United States)

    Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

    2017-04-12

    Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection with a large cohort of young adult participants (N = 257). Consistent with some previous human studies, we found that parental care in childhood alone had little association with the hippocampal volume in adulthood. However, when parental overprotection was low, parental care was positively correlated with offspring hippocampal volume, whereas there was no association between parental care and offspring hippocampal volume when parental overprotection was high. Thus, an interaction exists between parental care and overprotection in human's hippocampal development, which contributes to the elucidation of the complex relationship between brain structure and environmental factors.

  20. Associations of Maternal Pre-Pregnancy Body Mass Index and Gestational Weight Gain with Adult Offspring Cardio-Metabolic Risk Factors: The Jerusalem Perinatal Family Follow-up Study

    Science.gov (United States)

    Hochner, Hagit; Friedlander, Yechiel; Calderon-Margalit, Ronit; Meiner, Vardiella; Sagy, Yael; Avgil-Tsadok, Meytal; Burger, Ayala; Savitsky, Bella; Siscovick, David S.; Manor, Orly

    2012-01-01

    Background Accumulating evidence demonstrates that both maternal pre-pregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardio-metabolic risk factors in adulthood has not been comprehensively studied. Methods and Results We used a birth cohort of 1400 young adults born in Jerusalem, with extensive archival data as well as clinical information at age 32, to prospectively examine the associations of mppBMI and GWG with adiposity and related cardio-metabolic outcomes. Greater mppBMI, independent of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference (WC), systolic and diastolic BP, insulin and triglycerides and with lower HDL-C. For example, the effect sizes were translated to nearly 5kg/m2 higher mean BMI, 8.4cm higher WC, 0.13mmol/L (11.4mg/dL) higher triglycerides and 0.10mmol/L (3.8mg/dL) lower HDL-C among offspring of mothers within the upper mppBMI quartile (BMI>26.4kg/m2) compared to the lower (BMI14kg) and lower (GWG<9kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated to null the observed associations. Conclusions Maternal size both before and during pregnancy are associated with cardio-metabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardio-metabolic risk-reduction interventions. PMID:22344037

  1. The Transmission of Values to School-Age and Young Adult Offspring: Race and Gender Differences in Parenting

    Science.gov (United States)

    Pagano, Maria E.; Hirsch, Barton J.; Deutsch, Nancy L.; McAdams, Dan P.

    2003-01-01

    The current study explores parental socialization practices and the values transmitted to school-aged and young adult off-spring, focusing on race and gender issues involved in parental teachings. A community sample of 187 black and white mothers and fathers were interviewed with regards to their parenting practices using both quantitative and…

  2. The Effect of Opium Dependency of Parent (s) on Offspring's Spatial Learning & Memory in Adult Male Rats.

    Science.gov (United States)

    Saberi Moghadam, Arezoo; Sepehri, Gholamreza; Sheibani, Vahid; Haghpanah, Tahereh; Divsalar, Kouros; Hajzadeh, Mousa-Al-Reza; Afarineshkhaki, Mohammadreza

    2013-05-01

    As far as we know, there has been no report regarding the effects of opium addiction or dependency of both parents on the learning and memory process in offspring. The aim of this study was to examine the learning and memory changes of adult male offspring whose mothers, fathers and/or both parents had dependency to opium before and during pregnancy. Materials and Methods : All experiments were carried out on Wistar rats. Opium dependency was induced by daily injections of opium (10 mg/kg/SC, bid/10 d) before mating. The presence of a vaginal plug was designated as gestation day. Treatment with opium continued through breeding and gestation until parturition. Spatial memory was tested in male offspring of control, saline and prenatal opium treated groups by a training trial and the probe test in the Morris water maze. Swimming escape latency in the maze and the ability to find the platform in the training trial were recorded. The time spent in the trigger zone and number of times the rats crossed the platform during the probe phase and swimming speed were measured. The data revealed increased escape latency and a greater distance traveled to find the hidden platform in the offspring's whose mother, father and /or both parents were exposed to opium. Crossings to target quadrant at probe trials was significantly reduced in all of the prenatal opium exposed offsprings. The swimming speed showed a significant increase in father and parent's opium exposed offspring. Prenatal opium exposure of either parent may cause deficits in spatial learning, but the precise mechanism(s) remain largely unknown.

  3. Hyperglycaemia in pregnant rats causes sex-related vascular dysfunction in adult offspring: role of cyclooxygenase-2.

    Science.gov (United States)

    de Sá, Francine Gomes; de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; da Silva, Odair Alves; Moreira, Hicla Stefany; Leal, Geórgia Andrade; da Rocha, Marcelo Aurélio; Duarte, Gloria Pinto; Xavier, Fabiano Elias

    2017-08-01

    What is the central question of this study? Hyperglycaemia during pregnancy induces vascular dysfunction and hypertension in male offspring. Given that female offspring from other fetal programming models are protected from the effects of fetal insult, the present study investigated whether there are sex differences in blood pressure and vascular function in hyperglycaemia-programmed offspring. What is the main finding and its importance? We demonstrated that hyperglycaemia in pregnant rats induced vascular dysfunction and hypertension only in male offspring. We found sex differences in oxidative stress and cyclooxygenase-2-derived prostanoid production that might underlie the vascular dysfunction. These differences, particularly in resistance arteries, may in part explain the absence of hypertension in female offspring born to hyperglycaemic dams. Exposure to maternal hyperglycaemia induces hypertension and vascular dysfunction in adult male offspring. Given that female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analysed possible differences relative to sex in blood pressure and vascular function in hyperglycaemia-programmed offspring. Hyperglycaemia was induced on day 7 of gestation (streptozotocin, 50 mg kg -1 ). Blood pressure, acetylcholine and phenylephrine or noradrenaline responses were analysed in the aorta and mesenteric resistance arteries of 3-, 6- and 12-month-old male and female offspring. Thromboxane A 2 release was analysed with commercial kits and superoxide anion (O 2 - ) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had higher blood pressure than control animals (O-CR). Contraction in response to phenylephrine increased and relaxation in response to acetylcholine decreased only in the aorta from 12-month-old male O-DR and not in age-matched O-CR. Contractile and vasodilator responses were preserved in both the

  4. Associations between substance use disorders and major depression in parents and late adolescent-emerging adult offspring: an adoption study

    DEFF Research Database (Denmark)

    Marmorstein, N. R.; Iacono, W. G.; McGue, M.

    2012-01-01

    Aims To examine whether major depressive disorder (MDD) and substance use disorders [SUDs: specifically, nicotine dependence (ND), alcohol use disorders (AUDs), and cannabis use disorders (CUDs)] in parents predicted increased risk for these disorders in late adolescentemerging adult offspring and...

  5. Perceived parental rearing of bipolar offspring

    NARCIS (Netherlands)

    Reichart, C. G.; van der Ende, J.; Hillegers, M. H. J.; Wals, M.; Bongers, I. L.; Nolen, W. A.; Ormel, J.; Verhulst, F. C.

    Objective: To explore the impact of growing up with a parent with a bipolar disorder. First, we compared parental rearing behavior perceived by young adult offspring of bipolar parents with parental rearing behavior perceived by same aged young adults from the general population. Secondly, we

  6. Parental body mass index and blood pressure are associated with higher body mass index and blood pressure in their adult offspring: a cross-sectional study in a resource-limited setting in northern Peru.

    Science.gov (United States)

    Carrillo-Larco, Rodrigo M; Bernabé-Ortiz, Antonio; Sal Y Rosas, Víctor G; Sacksteder, Katherine A; Diez-Canseco, Francisco; Cárdenas, María K; Gilman, Robert H; Miranda, J Jaime

    2018-05-01

    High body mass index (BMI) and blood pressure (BP) are major contributors to the high burden of non-communicable diseases in adulthood. Individual high-risk and population approaches for prevention require newer strategies to target these risk factors and focusing on the family to introduce prevention initiatives appears as a promising scenario. Characterisation of the relationship between BMI and BP among the adult members of a given family merits evaluation. We conducted a secondary analysis of an implementation study in Tumbes, Peru, benefiting from data derived from families with at least one adult offspring. The exposures of interest were the BMI, systolic BP (SBP) and diastolic BP (DBP) of the mother and father. The outcomes were the BMI, SBP and DBP of the offspring. Mixed-effects linear regression models were conducted. The mean age of the offspring, mothers and fathers was 29 (SD: 9.5), 54 (SD: 11.8) and 59 (SD: 11.6) years, respectively. Father's BMI was associated with a quarter-point increase in offspring BMI, regardless of the sex of the offspring. Mother's BMI had a similar effect on the BMI of her sons, but had no significant effect on her daughters'. Mother's SBP was associated with almost one-tenth of mmHg increase in the SBP of the adult offspring. There was no evidence of an association for DBP. In families with adult members, the higher the parents' BMI and SBP, the higher their adult offspring's levels will be. © 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  7. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

    Directory of Open Access Journals (Sweden)

    Jean-François Gautier

    Full Text Available Fetal exposure to hyperglycemia impacts negatively kidney development and function.Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring.Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D (case group were matched with 28 offspring of T1D fathers (control group for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium. In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR and Effective Renal Plasma Flow (ERPF at baseline and during vasodilatation produced by amino acid infusion.Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls.Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

  8. Later Life Impacts of Social Participation on Parents of Adult Offspring with and without Intellectual and Developmental Disabilities

    Science.gov (United States)

    Olsen, Darren L.

    2018-01-01

    Social participation is an important resource for parents in old age, and may be particularly important for parents living with adult offspring with intellectual and developmental disabilities. To evaluate whether socializing with friends and family and participating in social organizations protects against depression in old age, this study…

  9. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  10. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  11. Sex-reversed somatic cell cloning in the mouse.

    Science.gov (United States)

    Inoue, Kimiko; Ogonuki, Narumi; Mekada, Kazuyuki; Yoshiki, Atsushi; Sado, Takashi; Ogura, Atsuo

    2009-10-01

    Somatic cell nuclear transfer has many potential applications in the fields of basic and applied sciences. However, it has a disadvantage that can never be overcome technically-the inflexibility of the sex of the offspring. Here, we report an accidental birth of a female mouse following nuclear transfer using an immature Sertoli cell. We produced a batch of 27 clones in a nuclear transfer experiment using Sertoli cells collected from neonatal male mice. Among them, one pup was female. This "male-derived female" clone grew into a normal adult and produced offspring by natural mating with a littermate. Chromosomal analysis revealed that the female clone had a 39,X karyotype, indicating that the Y chromosome had been deleted in the donor cell or at some early step during nuclear transfer. This finding suggests the possibility of resuming sexual reproduction after a single male is cloned, which should be especially useful for reviving extinct or endangered species.

  12. (Meta)cognitive beliefs in posttraumatic stress disorder following forced displacement at the end of the Second World War in older adults and their offspring.

    Science.gov (United States)

    Jelinek, Lena; Wittekind, Charlotte E; Kellner, Michael; Moritz, Steffen; Muhtz, Christoph

    2013-01-01

    The aim of the present study was to investigate (meta)cognitive beliefs related to posttraumatic stress disorder (PTSD) in a sample of individuals displaced as children at the end of the Second World War as well as transgenerational effects of trauma and PTSD on the offspring. Displaced individuals with (n=20) and without PTSD (n=24) and nondisplaced healthy controls (n=11), as well as one of their adult offspring, were assessed with the Metacognitions Questionnaire (MCQ-30). Older adults, formerly displaced in childhood, were additionally assessed with the Posttraumatic Cognitions Inventory (PTCI). Dysfunctional beliefs (MCQ-30, PTCI) were particularly pronounced in formerly displaced individuals with PTSD, but not in the offspring generation. The findings suggest that in an aging group of displaced individuals with PTSD dysfunctional beliefs are associated with the disorder. Bias modification may help to attenuate symptomatology. No evidence was found for a transgenerational effect.

  13. Parental Smoking and Adult Offspring's Smoking Behaviors in Ethnic Minority Groups: An Intergenerational Analysis in the HELIUS Study.

    Science.gov (United States)

    Ikram, Umar Z; Snijder, Marieke B; Derks, Eske M; Peters, Ron J G; Kunst, Anton E; Stronks, Karien

    2017-06-21

    To understand smoking behaviors among ethnic minority groups, studies have largely focused on societal factors, with little attention to family influences. Yet studies among majority groups have identified parental smoking as an important risk factor. It is unknown whether this applies to ethnic minority groups. We investigated the association between parental smoking and adult offspring's smoking behaviors among ethnic minority groups with an immigrant background. We used data from the Healthy Life in an Urban Setting study from Amsterdam (the Netherlands) from January 2011 to December 2015. The sample consisted of 2184 parent-offspring pairs from South-Asian Surinamese, African Surinamese, Turkish, Moroccan, and Ghanaian origin. We collected self-reported smoking data: current status, duration of exposure to parental smoking, number of daily cigarettes, heavy smoking ( > 10 cigarettes/day), and nicotine dependency (using the Fagerström Test). Analyses were stratified by offspring's age, cohabitation with parent, education (parent/offspring), offspring's cultural orientation, and gender concordance within pairs. Logistic regression was used. Overall, parental smoking was associated with offspring's smoking behaviors (eg, current smoking: odds ratio 2.33; 95% confidence interval 1.79-3.03), with little ethnic variation. We found dose-response associations between exposure to parental smoking and offspring's smoking. The associations were similar across different strata but stronger in gender-concordant pairs (3.16; 2.12-4.51 vs. 1.73; 1.15-2.59 in gender-discordant pairs; p-value for interaction .017). Parental smoking is associated with offspring's smoking behaviors in ethnic minority groups across different strata but particularly in gender-concordant pairs. Similar to majority groups, family influences matter to smoking behaviors in ethnic minority groups. Our findings have deepened our understanding of smoking behaviors among ethnic minority groups. Future

  14. Litter size reduction accentuates maternal care and alters behavioral and physiological phenotypes in rat adult offspring.

    Science.gov (United States)

    Enes-Marques, Silvia; Giusti-Paiva, Alexandre

    2018-01-27

    Maternal behavior has a substantial impact on the behavioral, endocrine, and neural development of the pups. This study investigated the effect of altering the neonatal nutritional environment by modifying the litter size on maternal care and anxiety- and fear-like behaviors in rats during adulthood. On postnatal day (PND) 2, litters were adjusted to a small litter (SL) size of three pups per dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors were scored daily during lactation (PND2-21). The weight gain, food intake, adiposity, and biochemical landmarks of offspring rats were evaluated. On PND60, performances in the open field, elevated plus-maze (EPM), and fear conditioning test were measured. The reduction of the litter size enhanced maternal care in lactating rats, increasing the arched-back posture and licking pups. SL offspring exhibited accelerated weight gain, hyperphagia, increased visceral fat mass, dyslipidemia, and hyperleptinemia in adulthood. The SL offspring of both sexes showed an increase in the anti-thigmotactic effect in the open field, an intact anxious-phenotype in the EPM, and a decrease in the time spent freezing during the fear-conditioning test, compared to NL. The neonatal environment as determined by litter size plays a crucial role in programming the adult metabolic phenotype as well as behavioral responses to stressful stimuli, with an impact on anxiety-like and fear behaviors. These behavioral changes in offspring may be, at least in part, a result of increased maternal care.

  15. Elevated paternal glucocorticoid exposure modifies memory retention in female offspring.

    Science.gov (United States)

    Yeshurun, Shlomo; Rogers, Jake; Short, Annabel K; Renoir, Thibault; Pang, Terence Y; Hannan, Anthony J

    2017-09-01

    Recent studies have demonstrated that behavioral traits are subject to transgenerational modification by paternal environmental factors. We previously reported on the transgenerational influences of increased paternal stress hormone levels on offspring anxiety and depression-related behaviors. Here, we investigated whether offspring sociability and cognition are also influenced by paternal stress. Adult C57BL/6J male mice were treated with corticosterone (CORT; 25mg/L) for four weeks prior to paired-matings to generate F1 offspring. Paternal CORT treatment was associated with decreased body weights of female offspring and a marked reduction of the male offspring. There were no differences in social behavior of adult F1 offspring in the three-chamber social interaction test. Despite male offspring of CORT-treated fathers displaying hyperactivity in the Y-maze, there was no observable difference in short-term spatial working memory. Spatial learning and memory testing in the Morris water maze revealed that female, but not male, F1 offspring of CORT-treated fathers had impaired memory retention. We used our recently developed methodology to analyze the spatial search strategy of the mice during the learning trials and determined that the impairment could not be attributed to underlying differences in search strategy. These results provide evidence for the impact of paternal corticosterone administration on offspring cognition and complement the cumulative knowledge of transgenerational epigenetic inheritance of acquired traits in rodents and humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The schooling of offspring and the survival of parents.

    Science.gov (United States)

    Friedman, Esther M; Mare, Robert D

    2014-08-01

    Contemporary stratification research on developed societies usually views the intergenerational transmission of educational advantage as a one-way effect from parent to child. However, parents' investment in their offspring's schooling may yield significant returns for parents themselves in later life. For instance, well-educated offspring have greater knowledge of health and technology to share with their parents and more financial means to provide for them than do their less-educated counterparts. We use data from the 1992-2006 Health and Retirement Study (HRS) to examine whether adult offspring's educational attainments are associated with parents' survival in the United States. We show that adult offspring's educational attainments have independent effects on their parents' mortality, even after controlling for parents' own socioeconomic resources. This relationship is more pronounced for deaths that are linked to behavioral factors: most notably, chronic lower respiratory disease and lung cancer. Furthermore, at least part of the association between offspring's schooling and parents' survival may be explained by parents' health behaviors, including smoking and physical activity. These findings suggest that one way to influence the health of the elderly is through their offspring. To harness the full value of schooling for health, then, a family and multigenerational perspective is needed.

  17. Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring

    Directory of Open Access Journals (Sweden)

    Anne-Maj eSamuelsson

    2013-02-01

    Full Text Available Eating an unbalanced diet during pregnancy may induce long-term health consequences in offspring, in particular obesity, insulin resistance and hypertension. We tested the hypothesis that a maternal diet rich in simple sugars predispose mouse offspring to obesity, glucose intolerance and cardiovascular diseases in adulthood.Female C57BL/6J mice were fed either a standard chow or a sucrose-rich diet (26% of total energy 6 weeks prior to mating, throughout pregnancy and lactation. Offspring of control dams (OC and high sucrose fed dams (OSF were weaned onto standard control chow, and metabolic and cardiovascular parameters determined at 3 months of age. Both male and female OSF were hyperphagic by 4 weeks of age and females were heavier than OC at 9 weeks. At 3 months, female OSF showed a significant increase in inguinal fat pad mass, whereas skeletal muscle mass (tibialis anterior and locomotor activity were decreased relative to OC. A ten-fold increase in fasting serum insulin in female OSF versus OC at 3 months (Insulin [pmol/L] mean±SEM, OSF, 200.3±16.1, versus OC, 20.3±1.8, n=6 P<0.001, was associated with impaired glucose tolerance (AUC [mmol/L min] mean±SEM, OSF 1437.4±124.2 versus OC, 1076.8±83.9, n=6, P<0.05. Both male and female OSF were hypertensive as assessed by radiotelemetry (night-time systolic arterial pressure [mmHg] mean±SEM, male OSF, 128±1 versus OC, 109±1, n=6, P<0.01; female OSF, 130±1 versus OC, 118±1, n=6, P<0.05. Analysis of heart rate variability demonstrated an increased low:high frequency ratio in male and female OSF (P<0.05, indicative of heightened sympathetic efferent tone. Renal tissue noradrenaline content was markely raised in the OSF versus OC (noradrenaline [pg/ml/mg tissue] mean±SEM, male OSF, 2.28±0.19 versus OC 0.84±0.09, n=6, P<0.01 . Exposure to a maternal diet rich in sucrose led to obesity and glucose intolerance in female mice offspring, and hypertension in both sexes.

  18. Gestational Exposure to a Viral Mimetic Poly(I:C Results in Long-Lasting Changes in Mitochondrial Function by Leucocytes in the Adult Offspring

    Directory of Open Access Journals (Sweden)

    Cecilia Giulivi

    2013-01-01

    Full Text Available Maternal immune activation (MIA is a potential risk factor for autism spectrum disorder (ASD and schizophrenia (SZ. In rodents, MIA results in changes in cytokine profiles and abnormal behaviors in the offspring that model these neuropsychiatric conditions. Given the central role that mitochondria have in immunity and other metabolic pathways, we hypothesized that MIA will result in a fetal imprinting that leads to postnatal deficits in the bioenergetics of immune cells. To this end, splenocytes from adult offspring exposed gestationally to the viral mimic poly(I:C were evaluated for mitochondrial outcomes. A significant decrease in mitochondrial ATP production was observed in poly(I:C-treated mice (45% of controls mainly attributed to a lower complex I activity. No differences were observed between the two groups in the coupling of electron transport to ATP synthesis, or the oxygen uptake under uncoupling conditions. Concanavalin A- (ConA- stimulated splenocytes from poly(I:C animals showed no statistically significant changes in cytokine levels compared to controls. The present study reports for the first time that MIA activation by poly(I:C at early gestation, which can lead to behavioral impairments in the offspring similar to SZ and ASD, leads to long-lasting effects in the bioenergetics of splenocytes of adult offspring.

  19. Mediators and moderators of parental alcoholism effects on offspring self-esteem.

    Science.gov (United States)

    Rangarajan, Sripriya

    2008-01-01

    The goal of the proposed study was fourfold: (i) to examine the effects of parental alcoholism on adult offspring's self-esteem; (ii) to identify and test possible mediators and moderators of parental alcoholism effects on the self-esteem of adult offspring; (iii) to examine the utility and relevance of attachment theory (Bowlby J. (1969) Attachment and Loss: Vol. 1. Attachment. New York: Basic Books) in explaining parental alcoholism effects on self-esteem and (iv) to address some of the methodological limitations identified in past research on adult children of alcoholics (ACOA). Participants (N = 515) completed retrospective reports of parental alcoholism, family stressors, family communication patterns, parental attachment and a current measure of self-esteem. The results showed support for the detrimental effects of parental alcoholism on offspring self-esteem and offered partial support for family stressors as a mediator of parental alcoholism effects on parental attachment and parental attachment as a mediator of parental alcoholism effects on offspring self-esteem, respectively. Finally, support was found for family communication patterns as a moderator of the effects of family stressors on attachment. The study findings offer preliminary support for the utility of attachment theory in explicating parental alcoholism effects on the self-esteem of adult offspring. Findings from the present study make salient the need to consider factors beyond the identification of parental alcohol abuse when explicating individual differences in offspring self-esteem in adulthood. The identification of protective and risk factors can contribute to the development of optimal intervention strategies to help ACOAs better than simply the knowledge of family drinking patterns.

  20. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    International Nuclear Information System (INIS)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M.

    2013-01-01

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g -1 ·min -1 ) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g -1 ·min -1 ) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring

  1. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M. [Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2013-03-15

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g{sup -1}·min{sup -1}) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g{sup -1}·min{sup -1}) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

  2. Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats.

    Science.gov (United States)

    Zhang, Xiaosong; Wang, Qi; Wang, Yan; Hu, Jingmin; Jiang, Han; Cheng, Wenwen; Ma, Yuchao; Liu, Mengxi; Sun, Anji; Zhang, Xinxin; Li, Xiaobai

    2016-12-01

    Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions

  3. Maternal intake of trans-unsaturated or interesterified fatty acids during pregnancy and lactation modifies mitochondrial bioenergetics in the liver of adult offspring in mice.

    Science.gov (United States)

    de Velasco, Patricia C; Chicaybam, Gustavo; Ramos-Filho, Dionizio M; Dos Santos, Raísa M A R; Mairink, Caroline; Sardinha, Fátima L C; El-Bacha, Tatiana; Galina, Antonio; Tavares-do-Carmo, Maria das Graças

    2017-07-01

    The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes for trans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich in trans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+ uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2 production was higher in the IG offspring. In addition, mitochondrial Ca2+ retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption of trans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.

  4. Gestational chronodisruption impairs hippocampal expression of NMDA receptor subunits Grin1b/Grin3a and spatial memory in the adult offspring.

    Directory of Open Access Journals (Sweden)

    Nelson Vilches

    Full Text Available Epidemiological and experimental evidence correlates adverse intrauterine conditions with the onset of disease later in life. For a fetus to achieve a successful transition to extrauterine life, a myriad of temporally integrated humoral/biophysical signals must be accurately provided by the mother. We and others have shown the existence of daily rhythms in the fetus, with peripheral clocks being entrained by maternal cues, such as transplacental melatonin signaling. Among developing tissues, the fetal hippocampus is a key structure for learning and memory processing that may be anticipated as a sensitive target of gestational chronodisruption. Here, we used pregnant rats exposed to constant light treated with or without melatonin as a model of gestational chronodisruption, to investigate effects on the putative fetal hippocampus clock, as well as on adult offspring's rhythms, endocrine and spatial memory outcomes. The hippocampus of fetuses gestated under light:dark photoperiod (12:12 LD displayed daily oscillatory expression of the clock genes Bmal1 and Per2, clock-controlled genes Mtnr1b, Slc2a4, Nr3c1 and NMDA receptor subunits 1B-3A-3B. In contrast, in the hippocampus of fetuses gestated under constant light (LL, these oscillations were suppressed. In the adult LL offspring (reared in LD during postpartum, we observed complete lack of day/night differences in plasma melatonin and decreased day/night differences in plasma corticosterone. In the adult LL offspring, overall hippocampal day/night difference of gene expression was decreased, which was accompanied by a significant deficit of spatial memory. Notably, maternal melatonin replacement to dams subjected to gestational chronodisruption prevented the effects observed in both, LL fetuses and adult LL offspring. Collectively, the present data point to adverse effects of gestational chronodisruption on long-term cognitive function; raising challenging questions about the consequences of

  5. The effects of breeding protocol in C57BL/6J mice on adult offspring behaviour.

    Directory of Open Access Journals (Sweden)

    Claire J Foldi

    Full Text Available Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10-12 days and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH. The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM. Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI of the acoustic startle response. We found that length of sire exposure (LSE had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour.

  6. Adrenocortical responses to offspring-directed threats in two open-nesting birds.

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    Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

    2009-07-01

    Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

  7. Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: a characterization of the BPH/5 mouse in postnatal life.

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    Sutton, Elizabeth F; Lob, Heinrich E; Song, Jiunn; Xia, YunWei; Butler, Scott; Liu, Chin-Chi; Redman, Leanne M; Sones, Jenny L

    2017-04-01

    Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes. Copyright © 2017 the American Physiological Society.

  8. Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

    Science.gov (United States)

    Gallant, S; Welch, L; Martone, P; Shalev, U

    2017-06-15

    Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The influence of parental divorce and alcohol abuse on adult offspring risk of lifetime suicide attempt in the United States.

    Science.gov (United States)

    Alonzo, Dana; Thompson, Ronald G; Stohl, Mahlki; Hasin, Deborah

    2014-05-01

    The influences of parental divorce and alcohol abuse on adult offspring lifetime suicide attempt have not been examined in national data. This study analyzed data from the 2001-2002 NESARC to estimate main and interaction effects of parental divorce and alcohol abuse on lifetime suicide attempt. Adjusted for controls, parental divorce and parental alcohol abuse independently increased odds of lifetime suicide attempt. The effect of parental divorce was not significantly moderated by parental alcohol abuse. Further research is needed to examine whether additional parental and offspring psychiatric and substance use covariates attenuate the association between parental divorce and lifetime suicide attempt. PsycINFO Database Record (c) 2014 APA, all rights reserved

  10. Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

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    Sérgio Gomes da Silva

    Full Text Available Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task. Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation and associative (spatial learning mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning and increases BDNF levels and cell numbers in the hippocampal formation of offspring.

  11. Ingestion of carbohydrate-rich supplements during gestation programs insulin and leptin resistance but not body weight gain in adult rat offspring

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    Bernard eBeck

    2012-06-01

    Full Text Available Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important hormonal status modification is a period of changes in usual feeding habits with pulses or avoidance for certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their intake with either a control (Cr, high-fat (HF, or high-carbohydrate (HC diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females ( -16%; p<0.001 and their offspring presented a weight deficit from birth until 6 (HC group and 10 (Cr group weeks of age (p<0.05 or less. Plasma leptin corresponded to low body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%;p<0.001, but plasma leptin and insulin were similar in their offspring. Hypothalamic Ob-Rb expression was increased in Cr, HC and HF offspring (+33-100% vs. Ca; p<0.05 or less. HC supplement ingestion during gestation leads therefore to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest to be heedful of the carbohydrate content in the diet during the last weeks (or months preceding delivery to limit development of later metabolic disorders in offspring.

  12. Administration of Rhodiola kirilowii Extracts during Mouse Pregnancy and Lactation Stimulates Innate but Not Adaptive Immunity of the Offspring

    Directory of Open Access Journals (Sweden)

    Sławomir Lewicki

    2017-01-01

    Full Text Available The use of antibiotics during pregnancy and lactation is associated with an increased risk of developmental disorders. One of the natural medicinal plants—Rhodiola kirilowii, widely used as an immunostimulant in adults—might be a good alternative to antibiotic treatment. The aim of present study was to assess whether daily oral administration of 20 mg/kg of Rhodiola kirilowii aqueous (RKW or 50% hydroalcoholic (RKW-A extracts affected hematological and immunological parameters of 6-week-old mouse progeny. There was no significant change in hematological parameters of blood with the exception of hemoglobin, which was significantly higher (about 4% in RKW group. Offspring of mothers fed Rhodiola kirilowii extracts had increased percentage of granulocytes and decreased percentage of lymphocytes. These changes correlated with decreased percentage of CD3+/CD4+ T-cells (RKW and RKW-A, decrease of CD8+ cells, and increase percentage of NK cells in RKW group. In addition, both types of Rhodiola kirilowii extracts stimulated granulocyte phagocytosis and increased level of respiratory burst. In conclusion, the long-term supplementation of mouse mothers during pregnancy and lactation with RKW or RKW-A extracts affects the immune system of their progeny. These results should be taken into consideration before administration of Rhodiola kirilowii to pregnant and lactating women.

  13. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring.

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    Rossini, Kamila Fernanda; Oliveira, Camila Andrea de; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-07-01

    The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. A limitação dietética durante a gravidez influencia o crescimento e desenvolvimento do feto e da prole e sua saúde na vida adulta. Os mecanismos subjacentes dos efeitos adversos da restrição proteica gestacional (RPG) no desenvolvimento dos corações da prole não são bem compreendidos. Avaliar os efeitos da RPG sobre a estrutura cardíaca em filhotes machos de ratas aos 60 dias após o nascimento (d60). Ratos fêmeas Wistar grávidas foram alimentadas com uma dieta de proteína normal (PN, 17% caseína) ou de baixa proteína (BP, caseína 6%). Os valores de pressão arterial (PA) de descendentes do sexo masculino de

  14. Identification and characterization of adult mouse meniscus stem/progenitor cells.

    Science.gov (United States)

    Gamer, Laura W; Shi, Rui Rui; Gendelman, Ashira; Mathewson, Dylan; Gamer, Jackson; Rosen, Vicki

    Meniscal damage is a common problem that accelerates the onset of knee osteoarthritis. Stem cell-based tissue engineering treatment approaches have shown promise in preserving meniscal tissue and restoring meniscal function. The purpose of our study was to identify meniscus-derived stem/progenitor cells (MSPCs) from mouse, a model system that allows for in vivo analysis of the mechanisms underlying meniscal injury and healing. MSPCs were isolated from murine menisci grown in explant culture and characterized for stem cell properties. Flow cytometry was used to detect the presence of surface antigens related to stem cells, and qRT-PCR was used to examine the gene expression profile of MSPCs. Major proteins associated with MSPCs were localized in the adult mouse knee using immunohistochemistry. Our data show that MSPCs have universal stem cell-like properties including clonogenicity and multi-potentiality. MSPCs expressed the mesenchymal stem cell markers CD44, Sca-1, CD90, and CD73 and when cultured had elevated levels of biglycan and collagen type I, important extracellular matrix components of adult meniscus. MSPC also expressed significant levels of Lox and Igf-1, genes associated with the embryonic meniscus. Localization studies showed staining for these same proteins in the superficial and outer zones of the adult mouse meniscus, regions thought to harbor endogenous repair cells. MSPCs represent a novel resident stem cell population in the murine meniscus. Analysis of MSPCs in mice will allow for a greater understanding of the cell biology of the meniscus, essential information for enhancing therapeutic strategies for treating knee joint injury and disease.

  15. Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Sawada, Naoki; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Nishigaito, Yuka; Saito, Yasuyuki; Murata, Yoji; Nibu, Ken-Ichi; Matozaki, Takashi

    2018-04-15

    In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Mother-offspring associations in northern muriquis, Brachyteles hypoxanthus.

    Science.gov (United States)

    Tolentino, Karynna; Roper, James J; Passos, Fernando C; Strier, Karen B

    2008-03-01

    Maternal care of offspring is ubiquitous among primates, but its duration varies across species due to factors such as dispersal patterns and social dynamics, which influence opportunities for and potential benefits of maternal investment in older offspring, respectively. We examined mother-offspring associations in wild northern muriquis (Brachyteles hypoxanthus), in which males are philopatric, females typically disperse before puberty, and social relationships among and between males and females are egalitarian. Associations were systematically recorded between ten mothers, each with two-six offspring in the study group, and all group members from August 2003-May 2004 at the RPPN-Feliciano Miguel Abdala in Minas Gerais, Brazil. Infants of both sexes received similarly high percentages of their mothers' association time. Mothers without infants also maintained strong associations with their youngest juvenile sons. Mothers did not spend consistently more time associating with either juvenile or adult sons than daughters. Our finding of non-preferential associations between muriqui mothers and their older male offspring suggests that extended maternal investment in offspring may be of minimal value in their egalitarian society compared with its value for species living in hierarchical societies.

  17. Moderate exercise during pregnancy in Wistar rats alters bone and body composition of the adult offspring in a sex-dependent manner.

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    Brielle V Rosa

    Full Text Available Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively. At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01 and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02; however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during

  18. Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice.

    Science.gov (United States)

    Rideout, Todd C; Movsesian, Cheryl; Tsai, Yi-Ting; Iqbal, Aadil; Raslawsky, Amy; Patel, Mulchand S

    2015-08-01

    In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. Because lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers. This study used the hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) mouse model to test the hypothesis that mothers supplemented with phytosterols during gestation and lactation would produce offspring with a more favorable lipid profile than offspring from unsupplemented mothers, despite having a genetic predisposition toward hypercholesterolemia. Sixteen female apoE(-/-) mice were randomly assigned to 2 diets fed throughout the gestation and lactation periods: a cholesterol-enriched diet (CH) (0.15%) or the cholesterol-enriched diet supplemented with phytosterols (CH/PS) (2%). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively, and liver cholesterol was analyzed by GC. Compared with the CH-fed dams at the end of lactation, phytosterol-supplemented dams displayed lower (P 0.05) in HDL cholesterol and triacylglycerol (TG) concentrations. Pups from phytosterol-fed dams demonstrated lower (P 0.05) in HDL cholesterol compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from phytosterol-supplemented dams displayed a lower (P phytosterols during gestation and lactation exhibit favorable liver and serum lipid responses compared with pups from unsupplemented mothers. © 2015 American Society for Nutrition.

  19. Gene expression in the mouse brain following early pregnancy exposure to ethanol

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    Christine R. Zhang

    2016-12-01

    Full Text Available Exposure to alcohol during early embryonic or fetal development has been linked with a variety of adverse outcomes, the most common of which are structural and functional abnormalities of the central nervous system [1]. Behavioural and cognitive deficits reported in individuals exposed to alcohol in utero include intellectual impairment, learning and memory difficulties, diminished executive functioning, attention problems, poor motor function and hyperactivity [2]. The economic and social costs of these outcomes are substantial and profound [3,4]. Improvement of neurobehavioural outcomes following prenatal alcohol exposure requires greater understanding of the mechanisms of alcohol-induced damage to the brain. Here we use a mouse model of relatively moderate ethanol exposure early in pregnancy and profile gene expression in the hippocampus and caudate putamen of adult male offspring. The effects of offspring sex and age on ethanol-sensitive hippocampal gene expression were also examined. All array data are available at the Gene Expression Omnibus (GEO repository under accession number GSE87736.

  20. Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

    International Nuclear Information System (INIS)

    Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

    2017-01-01

    Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP

  1. Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

    Energy Technology Data Exchange (ETDEWEB)

    Pocar, Paola, E-mail: paola.pocar@unimi.it; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

    2017-05-01

    Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP

  2. Altered reward sensitivity in female offspring of cocaine-exposed fathers.

    Science.gov (United States)

    Fischer, Delaney K; Rice, Richard C; Martinez Rivera, Arlene; Donohoe, Mary; Rajadhyaksha, Anjali M

    2017-08-14

    Recent rodent studies have demonstrated that parental cocaine exposure can influence offspring behavior, supporting the idea that environmental insults can impact subsequent generations. However, studies on the effects of paternal cocaine exposure are limited and multiple inconsistencies exist. In the current study, we behaviorally characterize the effects of paternal cocaine exposure in a C57BL/6J intergenerational mouse model. Male sires were administered cocaine hydrochloride (20mg/kg) or saline (0.01mL/g) once a day for 75days, and bred with drug naïve females twenty-four hours after the final injection. Offspring, separated by sex, were tested in a battery of behaviors. We found that paternal cocaine exposure altered sensitivity to the rewarding and stimulant effects of psychostimulants and natural reward (sucrose) in female offspring; female cocaine-sired offspring showed blunted cocaine preference using cocaine conditioned place preference (CPP) at a low dose (5mg/kg), but displayed similar preference at a higher dose (10mg/kg) compared to saline-sired controls. Additionally, cocaine-sired female offspring exhibited higher psychomotor sensitivity to cocaine (10mg/kg) and amphetamine (2mg/kg) and consumed more sucrose. Cocaine-sired males exhibited increased psychomotor effects of cocaine and amphetamine. Male offspring also displayed an anxiety-like phenotype. No effect of paternal cocaine exposure was observed on depressive-like, learning and memory or social behavior in male or female offspring. Collectively, our findings show that paternal, chronic cocaine exposure induces intergenerational behavioral effects in male and female offspring with greatest impact on sensitivity to psychostimulants and sucrose in females. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Body size and intelligence in 6-year-olds: are offspring of teenage mothers at risk?

    Science.gov (United States)

    Cornelius, Marie D; Goldschmidt, Lidush; Willford, Jennifer A; Leech, Sharon L; Larkby, Cynthia; Day, Nancy L

    2009-11-01

    Children born to teenage mothers are at risk for more physical and cognitive problems than those born to adult mothers. Our objective was to examine differences in size and intelligence between two cohorts of offspring born to adolescent (n = 357) and adult mothers (n = 668) who attended the same prenatal clinic. Two prospective study cohorts assessed children from gestation through age 6 years. The adult cohort was studied in the mid-1980's and the teen cohort was evaluated in the mid-1990's. Both samples were of low socio-economic status. The same study design and measures allowed us to adjust for the covariates of size and IQ. Offspring of adolescent mothers had a significantly smaller mean head circumference (5 mm) (HC) and higher body mass index (BMI) than offspring of adult mothers. Offspring of adolescent mothers scored significantly lower than the offspring of adult mothers on the Stanford-Binet (SBIS) composite score (4 points), and the quantitative (6.2 points), verbal reasoning (4.8 points), and short-term memory (3.9 points) area scores. Additional predictors of child IQ were maternal IQ, home environment, race, and number of siblings. When child HC was entered into our final regression model for the SBIS, maternal age and HC significantly predicted the composite score, the verbal reasoning, and short-term memory area scores. A 1 cm decrease in HC predicted a 1 point decrease in the SBIS composite score. Compared to offspring of adult women, children of adolescent mothers have lower mean scores on cognitive measures, smaller head circumference, and higher BMI. These differences were significant after adjusting for differences between the two groups. Adolescent mothers and their children would benefit from interventions such as parenting support, education about nutritional needs, and advice on enriching the environments of their children.

  4. Maternal age at Holocaust exposure and maternal PTSD independently influence urinary cortisol levels in adult offspring

    Directory of Open Access Journals (Sweden)

    Heather N Bader

    2014-07-01

    Full Text Available Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal PTSD appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: 95 Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 hour urinary cortisol was assayed by RIA. Offspring completed the Parental PTSD Questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusions: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased risk for stress

  5. Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring

    Science.gov (United States)

    Bader, Heather N.; Bierer, Linda M.; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

    2014-01-01

    Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 h urinary cortisol was assayed by RIA. Offspring completed the parental PTSD questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence, or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusion: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased

  6. Parental problem drinking and anxiety disorder symptoms in adult offspring: examining the mediating role of anxiety sensitivity components.

    Science.gov (United States)

    MacPherson, P S; Stewart, S H; McWilliams, L A

    2001-01-01

    Preliminary studies have implicated childhood exposure to parental problem drinking as a possible factor in the development of anxiety sensitivity (AS). The present retrospective study was designed to examine the role of exposure to distressing parental problem drinking behaviors, over and above the role of parental alcoholism, in the development of various AS components (psychological, physical, and social concerns) in the offspring. We also examined the possible mediating role of AS components in explaining relations between parental drinking problems and anxiety-related symptoms in the adult offspring. A sample of 213 university students provided retrospective reports of both distress related to parental drinking [Children of Alcoholics Screening Test (CAST)] and parental alcoholism [maternal and paternal forms of the Short Michigan Alcoholism Screening Test (SMAST)]. Participants also reported on their own current AS levels [AS Index (ASI)], general anxiety symptoms [State-Trait Anxiety Inventory-Trait subscale (STAI-T)], and lifetime history of uncued panic attacks [Panic Attack Questionnaire-Revised (PAQ-R)]. Scores on the CAST predicted AS psychological and physical concerns (but not social concerns) over and above participant gender and parental alcoholism measured by the SMASTs. Moreover, AS psychological concerns proved a consistent modest mediator of the relations between parental problem drinking on the CAST and both general anxiety and uncued panic outcomes in the offspring. Thus, exposure to distressing parental problem drinking behavior may be one factor that contributes to elevated AS psychological concerns in the child, which in turn may contribute to the development of anxiety disorder symptoms in the offspring.

  7. Maternal Melatonin Therapy Attenuated Maternal High-Fructose Combined with Post-Weaning High-Salt Diets-Induced Hypertension in Adult Male Rat Offspring

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2018-04-01

    Full Text Available Consumption of food high in fructose and salt is associated with the epidemic of hypertension. Hypertension can originate from early life. Melatonin, a pleiotropic hormone, regulates blood pressure. We examined whether maternal melatonin therapy can prevent maternal high-fructose combined with post-weaning high-salt diet-induced programmed hypertension in adult offspring. Pregnant Sprague-Dawley rats received either a normal diet (ND or a 60% fructose diet (HF during pregnancy and the lactation period. Male offspring were on either the ND or a high-salt diet (HS, 1% NaCl from weaning to 12 weeks of age and were assigned to five groups (n = 8/group: ND/ND, HF/ND, ND/HS, HF/HS, and HF/HS+melatonin. Melatonin (0.01% in drinking water was administered during pregnancy and lactation. We observed that maternal HF combined with post-weaning HS diets induced hypertension in male adult offspring, which was attenuated by maternal melatonin therapy. The beneficial effects of maternal melatonin therapy on HF/HS-induced hypertension related to regulating several nutrient-sensing signals, including Sirt1, Sirt4, Prkaa2, Prkab2, Pparg, and Ppargc1a. Additionally, melatonin increased protein levels of mammalian targets of rapamycin (mTOR, decreased plasma asymmetric dimethylarginine (ADMA and symmetric dimethylarginine levels, and increased the l-arginine-to-ADMA ratio. The reprogramming effects by which maternal melatonin therapy protects against hypertension of developmental origin awaits further elucidation.

  8. Maternal Phytosterol Supplementation during Pregnancy and Lactation Modulates Lipid and Lipoprotein Response in Offspring of apoE-Deficient Mice123

    Science.gov (United States)

    Rideout, Todd C; Movsesian, Cheryl; Tsai, Yi-Ting; Iqbal, Aadil; Raslawsky, Amy; Patel, Mulchand S

    2015-01-01

    Background: In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. Because lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers. Objective: This study used the hypercholesterolemic apolipoprotein E–deficient (apoE−/−) mouse model to test the hypothesis that mothers supplemented with phytosterols during gestation and lactation would produce offspring with a more favorable lipid profile than offspring from unsupplemented mothers, despite having a genetic predisposition toward hypercholesterolemia. Methods: Sixteen female apoE−/− mice were randomly assigned to 2 diets fed throughout the gestation and lactation periods: a cholesterol-enriched diet (CH) (0.15%) or the cholesterol-enriched diet supplemented with phytosterols (CH/PS) (2%). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively, and liver cholesterol was analyzed by GC. Results: Compared with the CH-fed dams at the end of lactation, phytosterol-supplemented dams displayed lower (P 0.05) in HDL cholesterol and triacylglycerol (TG) concentrations. Pups from phytosterol-fed dams demonstrated lower (P 0.05) in HDL cholesterol compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from phytosterol-supplemented dams displayed a lower (P phytosterols during gestation and lactation exhibit favorable liver and serum lipid responses compared with pups from unsupplemented mothers. PMID:26084365

  9. Parental Divorce and Interpersonal Trust in Adult Offspring.

    Science.gov (United States)

    King, Valarie

    2002-01-01

    Examines whether parental divorce is associated with offspring trust in parents, intimate partners, and others. Results reveal that although parental divorce is negatively associated with trust, these effects largely disappear once the quality of the past parent-teen relationship is taken into account. (Contains 48 references and 4 tables.) (GCP)

  10. Maternal melatonin programs the daily pattern of energy metabolism in adult offspring.

    Directory of Open Access Journals (Sweden)

    Danilo S Ferreira

    Full Text Available BACKGROUND: Shift work was recently described as a factor that increases the risk of Type 2 diabetes mellitus. In addition, rats born to mothers subjected to a phase shift throughout pregnancy are glucose intolerant. However, the mechanism by which a phase shift transmits metabolic information to the offspring has not been determined. Among several endocrine secretions, phase shifts in the light/dark cycle were described as altering the circadian profile of melatonin production by the pineal gland. The present study addresses the importance of maternal melatonin for the metabolic programming of the offspring. METHODOLOGY/PRINCIPAL FINDINGS: Female Wistar rats were submitted to SHAM surgery or pinealectomy (PINX. The PINX rats were divided into two groups and received either melatonin (PM or vehicle. The SHAM, the PINX vehicle and the PM females were housed with male Wistar rats. Rats were allowed to mate and after weaning, the male and female offspring were subjected to a glucose tolerance test (GTT, a pyruvate tolerance test (PTT and an insulin tolerance test (ITT. Pancreatic islets were isolated for insulin secretion, and insulin signaling was assessed in the liver and in the skeletal muscle by western blots. We found that male and female rats born to PINX mothers display glucose intolerance at the end of the light phase of the light/dark cycle, but not at the beginning. We further demonstrate that impaired glucose-stimulated insulin secretion and hepatic insulin resistance are mechanisms that may contribute to glucose intolerance in the offspring of PINX mothers. The metabolic programming described here occurs due to an absence of maternal melatonin because the offspring born to PINX mothers treated with melatonin were not glucose intolerant. CONCLUSIONS/SIGNIFICANCE: The present results support the novel concept that maternal melatonin is responsible for the programming of the daily pattern of energy metabolism in their offspring.

  11. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring?

    DEFF Research Database (Denmark)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte

    2013-01-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring.......It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring....

  12. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.

    Science.gov (United States)

    McKee, Sarah E; Grissom, Nicola M; Herdt, Christopher T; Reyes, Teresa M

    2017-06-01

    During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life-particularly within the prefrontal cortex (PFC), a brain region critical for executive function-we examined whether early life methyl donor supplementation ( e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.-McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters

  13. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet–fed dams

    Science.gov (United States)

    McKee, Sarah E.; Grissom, Nicola M.; Herdt, Christopher T.; Reyes, Teresa M.

    2017-01-01

    During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)–fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life—particularly within the prefrontal cortex (PFC), a brain region critical for executive function—we examined whether early life methyl donor supplementation (e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.—McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation

  14. DNA methylation and gene expression of TXNIP in adult offspring of women with diabetes in pregnancy.

    Directory of Open Access Journals (Sweden)

    Azadeh Houshmand-Oeregaard

    Full Text Available Fetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM, possibly mediated by epigenetic mechanisms. Low blood TXNIP DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle TXNIP gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action. The extent to which TXNIP DNA methylation levels are decreased and/or gene expression levels increased in SAT or skeletal muscle of a developmentally programmed at-risk population is unknown.The objective of this study was to investigate TXNIP DNA methylation and gene expression in SAT and skeletal muscle, and DNA methylation in blood, from adult offspring of women with gestational diabetes (O-GDM, n = 82 or type 1 diabetes (O-T1DM, n = 67 in pregnancy compared with offspring of women from the background population (O-BP, n = 57.SAT TXNIP DNA methylation was increased (p = 0.032 and gene expression decreased (p = 0.001 in O-GDM, but these differences were attenuated after adjustment for confounders. Neither blood/muscle TXNIP DNA methylation nor muscle gene expression differed between groups.We found no evidence of decreased TXNIP DNA methylation or increased gene expression in metabolic target tissues of offspring exposed to maternal diabetes. Further studies are needed to confirm and understand the paradoxical SAT TXNIP DNA methylation and gene expression changes in O-GDM subjects.

  15. Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1) TAg mice offspring

    International Nuclear Information System (INIS)

    Ion, Gabriela; Akinsete, Juliana A; Hardman, W Elaine

    2010-01-01

    Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet) or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet). After two weeks on the diets the females were bred with homozygous C3(1) TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet. Compared to offspring of mothers fed the corn oil diet (CO/CO group), offspring of mothers fed the canola oil diet (CA/CO group) had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity); the tumor incidence (fraction of mice with any tumor) and the total tumor weight (per mouse that developed tumor) was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed. Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter

  16. Blood pressure pattern of adolescent offsprings of hypertensive ...

    African Journals Online (AJOL)

    Blood pressure pattern of adolescent offsprings of hypertensive fathers in Lagos ... in adults which emphasizes the need to track blood pressure in children. ... are hypertensive while among adolescents with normotensive parents, 11.0% for ...

  17. Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment

    Science.gov (United States)

    Plant, Dominic T.; Pariante, Carmine M.; Sharp, Deborah; Pawlby, Susan

    2015-01-01

    Background Studies have shown that maternal depression during pregnancy predicts offspring depression in adolescence. Child maltreatment is also a risk factor for depression. Aims To investigate (a) whether there is an association between offspring exposure to maternal depression in pregnancy and depression in early adulthood, and (b) whether offspring child maltreatment mediates this association. Method Prospectively collected data on maternal clinical depression in pregnancy, offspring child maltreatment and offspring adulthood (18–25 years) DSM-IV depression were analysed in 103 mother–offspring dyads of the South London Child Development Study. Results Adult offspring exposed to maternal depression in pregnancy were 3.4 times more likely to have a DSM-IV depressive disorder, and 2.4 times more likely to have experienced child maltreatment, compared with non-exposed offspring. Path analysis revealed that offspring experience of child maltreatment mediated the association between exposure to maternal depression in pregnancy and depression in adulthood. Conclusions Maternal depression in pregnancy is a key vulnerability factor for offspring depression in early adulthood. PMID:26045352

  18. MicroRNA expression in the adult mouse central nervous system

    DEFF Research Database (Denmark)

    Bak, Mads; Silahtaroglu, Asli; Møller, Morten

    2008-01-01

    distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

  19. Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

    Science.gov (United States)

    Lanham, S A; Cagampang, F R; Oreffo, R O C

    2014-12-01

    Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

  20. A mammalian spot test: induction of genetic alterations in pigment cells or mouse embryos with X-rays and chemical mutagens

    International Nuclear Information System (INIS)

    Fahrig, R.

    1975-01-01

    Embryos heterozygous for five recessive coat-color genes from the cross C57 BL/6 J Han x T-stock were X-irradiated with 100 r or treated in utero with 50 mg/kg methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), respectively. Controls consisted of irradiated embryos of C57 BL x C57 BL matings homozygous wild-type for the genes under study, and non-treated offspring of both types of mating. The colors of the spots observed in the adult fur were either due to expression of the recessive coat genes or were white. 1) Irradiated and mutagen-treated offspring of C57 BL x T-stock matings had almost exclusively nonwhite spots, distributed randomly over the mouse surface. 2) Irradiated offspring of C57 BL x C57 BL matings had only white spots which were always midventral. 3) In non-treated offspring of both types of mating no spot could be observed. It is discussed that the white midventral spots are preferentially the result of pigment cell killing, while the nonwhite spots are preferentially the result of gene mutations or recombinational processes like mitotic crossing over and mitotic gene conversion. (orig./BSC) [de

  1. The Effect of Preconception Paternal Alcohol Exposure on Epigenetic Remodelling of the H19 and Rasgrf1 Imprinting Control Regions in Mouse Offspring

    Directory of Open Access Journals (Sweden)

    Jaysen Gregory Knezovich

    2012-02-01

    Full Text Available Imprinted loci play a critical role in fetal development. Their expression is often regulated by CTCF protein binding at imprinting control regions (ICRs. Parental alcohol exposure has been shown to reduce global DNA methylation in the developing mouse fetus. This study explored the effect of preconception paternal alcohol exposure on DNA methylation at two paternally methylated ICRs (H19 and Rasgrf1 in the sperm of exposed males and somatic DNA of sired offspring. Significant reductions at the H19 CTCF 1 (p=0.0027 and CTCF 2 (p=0.0009 binding sites were observed in the offspring of ethanol-treated sires, which was significantly correlated with reduced weight at postnatal days 35 to 42 (p<0.05. As birth weight was unaffected and growth was only delayed during the postnatal weaning period, with subsequent re-convergence, we hypothesise that this may be the result of a mental deficit causing delayed establishment of independent feeding following weaning and would explain why this effect is transient. No difference in DNA methylation was observed in the sperm of alcohol-exposed males, indicating that the transmission of the epigenetic signal at conception is not due to altered methylation, but may be the result of an RNA-mediated mechanism or altered chromatin remodelling.

  2. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Δ9-tetrahydrocannabinol

    International Nuclear Information System (INIS)

    Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo; Lourdusamy, Anbarasu; Soverchia, Laura; Hardiman, Gary; Campolongo, Patrizia; Cuomo, Vincenzo; Ciccocioppo, Roberto

    2007-01-01

    The present study evaluated the consequences of perinatal Δ 9 -tetrahydrocannabinol (Δ 9 -THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB 1 receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Δ 9 -tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Δ 9 -THC, or EtOH + Δ 9 -THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Δ 9 -THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB 1 receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism

  3. Contextual risks linking parents' adolescent marijuana use to offspring onset.

    Science.gov (United States)

    Kerr, David C R; Tiberio, Stacey S; Capaldi, Deborah M

    2015-09-01

    We studied the extent to which parent marijuana use in adolescence is associated with marijuana use onset in offspring through contextual family and peer risks. Fathers assessed (n=93) since childhood, their 146 offspring (n=83 girls), and offspring's mothers (n=85) participated in a longitudinal study. Using discrete-time survival analysis, fathers' (prospectively measured) and mothers' (retrospective) adolescent marijuana use was used to predict offspring marijuana use onset through age 19 years. Parental monitoring, child exposure to marijuana use, peer deviance, peer marijuana use, and perceptions of parent disapproval of child use were measured before or concurrent with onset. Parents' adolescent marijuana use was significantly associated with less monitoring, offspring alcohol use, the peer behaviors, exposure to adult marijuana use, and perceptions of less parent disapproval. Male gender and the two peer behaviors were positively associated with children's marijuana use onset, controlling for their alcohol use. Parents' adolescent marijuana use had a significant indirect effect on child onset through children's deviant peer affiliations and a composite contextual risk score. Parents' histories of marijuana use may contribute indirectly to children's marijuana use onset through their influence on the social environments children encounter; specifically, those characterized by more liberal use norms, exposure to marijuana use and deviant and marijuana-using peers, and less adult supervision. Given that alcohol use onset was controlled, findings suggest that the contextual factors identified here confer unique risk for child marijuana use onset. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Risk of emotional disorder in offspring of depressed parents : Gender differences in the effect of a second emotionally affected parent

    NARCIS (Netherlands)

    Landman-Peeters, K.M.; Ormel, J.; van Sonderen, E.L.; den Boer, J.A.; Minderaa, R.B.; Hartman, C.A.

    2008-01-01

    In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring

  5. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    Science.gov (United States)

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

    Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

  6. Filial anxiety and sense of obligation among offspring of Holocaust survivors.

    Science.gov (United States)

    Shrira, Amit; Menashe, Ravit; Bensimon, Moshe

    2018-03-13

    Much is known about adult children caring for their aging parents, yet the potentially unique experience of offspring caring for traumatized parents is underexplored. Therefore, the current studies assessed filial anxiety and sense of obligation among offspring of Holocaust survivors (OHS) in caring for their parents. In Study 1, we interviewed 10 OHS (mean age = 61.0) in order to extract themes of filial anxiety. Based on Study 1's data, a newly constructed scale of filial anxiety was administered in Study 2 to 59 adult offspring (mean age = 56.4): 28 OHS and 31 comparisons. Study 3 included 143 dyads of parents and offspring (mean age = 55.4 and 81.7, respectively): 86 Holocaust dyads and 57 comparison dyads. Parents reported posttraumatic stress disorder (PTSD) symptoms and offspring reported filial anxiety and sense of obligation. In Study 1, interviewees referred to concerns about parent experiencing decline alongside caregiving difficulties. In Study 2, OHS reported higher filial anxiety and sense of obligation relative to comparisons. This group difference was mediated by sense of obligation. In Study 3, OHS with parental PTSD reported higher filial anxiety and sense of obligation relative to comparisons. Once more, filial sense of obligation served as a mediator. In Studies 2-3, results remained significant after adjusting for offspring symptoms. Parental exposure to the Holocaust, and especially parental PTSD, related to higher filial obligation, which in turn was related to higher filial anxiety. These findings bear important implications for practitioners working with survivors' families.

  7. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring? A prospective study over two decades.

    Science.gov (United States)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte; Hammer Bech, Bodil; Brink Henriksen, Tine; Vaag, Allan Arthur; Olsen, Sjurdur Frodi

    2013-08-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring. Longitudinal study where 965 pregnant women during 1988-1989 had four dimensions of PA assessed by questionnaires in gestation week 30: PA at work; leisure time PA, daily amount of walking-biking and sport participation. The following MS markers were assessed in the offspring (n=439): body mass index (BMI), waist circumference, blood pressure, homeostasis model assessment insulin resistance as well as fasting plasma glucose, triglycerides, cholesterol (high-density lipoprotein (HDL), low-density lipoprotein and total cholesterol), insulin and leptin levels. Walking-biking PA in pregnancy is associated with unchanged or subtle, adverse changes of distinct MS markers among offspring including lower levels of HDL cholesterol (ratio 0.95 (95% CI 0.92 to 0.98) per 1 h increment in walking-biking), a higher diastolic blood pressure (difference 1.12 (95% CI 0.03 to 2.20) mm Hg/1 h increment) and a higher BMI (ratio 1.03 (95% CI 1.01 to 1.05) per 1 h increment). In separate analyses in males, these associations persisted and additional adverse associations were found for triglycerides, systolic blood pressure, waist circumference and leptin. No associations were detected with other measures of PA. The study did not substantiate any protective effects of PA in pregnancy. In contrast, data suggested that high amounts of daily walking-biking in pregnancy may have adverse effects on levels of HDL cholesterol, diastolic blood pressure and BMI in young adult offspring.

  8. The Effects of the Preconception Endurance Exercise Training and Voluntary Exercise Activity during Pregnancy in C57BL/6 Mice on Lipid Profile of the Adult Offsprings

    Directory of Open Access Journals (Sweden)

    Abbasali Gaeini

    2016-05-01

    Full Text Available Abstract Background: The aim of this study was to determine the effect of preconception endurance exercise training with voluntary exercise activity during pregnancy in mother mice on lipid profile in adult offsprings. Materials and Methods: Twenty four C57BL/6 female mice were randomly divided into four subgroups: trained in preconception period and exercised during pregnancy (TE(20.3±1.02g; trained in preconception periods but unexercised during pregnancy (TC(21.58±0.4g; untrained in preconception periods but exercised during pregnancy (CE(21.02±0.23g; untrained and unexercised (CC(19.23±0.45g. Trained mice were subjected to a protocol of moderate endurance exercise training over a period of 4 weeks for 5 days before pregnancy. The fasting blood samples were collected from adult mice(8 weeks old and serum levels of glucose and lipid profile were measured. Data were analyzed using two way ANOVA and Tukey’s post hoc test. Results: The Glucose test results in offspring showed that there was a significant interaction between group and sex and group main effect (p<0.001 Glucose levels of male offspring were significantly lower in TC and TE groups. Results on LDL also showed that the sex main effect was significant (p<0.001, and LDL levels of male born to TE and TC dams lower than in female offspring. Conclusion: Improving the mother's physical fitness by providing regular endurance training in the preconception period and maintaining it by exercise activty throughout pregnancy may have potential for eliciting positive changes in lipid profile of offspring, specially males.

  9. Habitat structure influences parent-offspring association in a social lizard

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    Thomas Botterill-James

    2016-08-01

    Full Text Available Parental care emerges as a result of an increase in the extent of interaction between parents and their offspring. These interactions can provide the foundation for the evolution of a range of complex parental behaviors. Therefore, fundamental to understanding the evolution of parental care is an understanding of the factors that promote this initial increase in parent-offspring association. Here, we used large outdoor enclosures to test how the spatial structure of high-quality habitat affects the occurrence of parent-offspring associations in a social lizard (Liopholis whitii. We found that the extent of parent-offspring association was higher when high-quality habitat was aggregated relative to when it was dispersed. This may be the result of greater competitive exclusion of adults and offspring from high quality crevices sites in the aggregated treatment compared to the dispersed treatment. Associating with parents had significant benefits for offspring growth and body condition but there were no concomitant effects on offspring survival. We did not find costs of parent-offspring association for parents in terms of increased harassment and loss of body condition. We discuss a number of potential mechanisms underlying these results. Regardless of mechanisms, our results suggest that habitat structure may shape the extent of parent-offspring association in L. whitti, and that highly aggregated habitats may set the stage for the diversification of more complex forms of care observed across closely related species.

  10. Low folate and selenium in the mouse maternal diet alters liver gene expression patterns in the offspring after weaning.

    Science.gov (United States)

    Barnett, Matthew P G; Bermingham, Emma N; Young, Wayne; Bassett, Shalome A; Hesketh, John E; Maciel-Dominguez, Anabel; McNabb, Warren C; Roy, Nicole C

    2015-05-08

    During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.

  11. Low Folate and Selenium in the Mouse Maternal Diet Alters Liver Gene Expression Patterns in the Offspring after Weaning

    Directory of Open Access Journals (Sweden)

    Matthew P.G. Barnett

    2015-05-01

    Full Text Available During pregnancy, selenium (Se and folate requirements increase, with deficiencies linked to neural tube defects (folate and DNA oxidation (Se. This study investigated the effect of a high-fat diet either supplemented with (diet H, or marginally deficient in (diet L, Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis, methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.

  12. Infectious offspring: how birds acquire and transmit an avian polyomavirus in the wild.

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    Jaime Potti

    Full Text Available Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an 'upwards vertical' route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care.

  13. Maternal dietary loads of alpha-tocopherol increase synapse density and glial synaptic coverage in the hippocampus of adult offspring

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    S. Salucci

    2014-05-01

    Full Text Available An increased intake of the antioxidant α-Tocopherol (vitamin E is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Glia-synapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses was increased. These findings indicate that gestational and neonatal exposure to supranutritional tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant glia-synapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning.

  14. Risk of Suicide Attempt in Adopted and Nonadopted Offspring

    DEFF Research Database (Denmark)

    Keyes, M. A.; Malone, S. M.; Sharma, A.

    2013-01-01

    OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide att...... of the risk of suicide attempt in adopted offspring may inform the larger investigation of suicidality in all adolescents and young adults.......OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt for adopted and nonadopted offspring living in the United States. We also examined whether factors known to be associated with suicidal behavior would mediate the relationship between adoption status and suicide...... attempt. METHODS: Participants were drawn from the Sibling Interaction and Behavior Study, which included 692 adopted and 540 nonadopted offspring and was conducted at the University of Minnesota from 1998 to 2008. Adoptees were systematically ascertained from records of 3 large Minnesota adoption...

  15. Prenatal Metformin Therapy Attenuates Hypertension of Developmental Origin in Male Adult Offspring Exposed to Maternal High-Fructose and Post-Weaning High-Fat Diets

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    You-Lin Tain

    2018-04-01

    Full Text Available Widespread consumption of a Western diet, comprised of highly refined carbohydrates and fat, may play a role in the epidemic of hypertension. Hypertension can take origin from early life. Metformin is the preferred treatment for type 2 diabetes. We examined whether prenatal metformin therapy can prevent maternal high-fructose plus post-weaning high-fat diets-induced hypertension of developmental origins via regulation of nutrient sensing signals, uric acid, oxidative stress, and the nitric oxide (NO pathway. Gestating Sprague–Dawley rats received regular chow (ND or chow supplemented with 60% fructose diet (HFR throughout pregnancy and lactation. Male offspring were onto either the ND or high-fat diet (HFA from weaning to 12 weeks of age. A total of 40 male offspring were assigned to five groups (n = 8/group: ND/ND, HFR/ND, ND/HFA, HFR/HFA, and HFR/HFA+metformin. Metformin (500 mg/kg/day was administered via gastric gavage for three weeks during the pregnancy period. Combined maternal HFR plus post-weaning HFA induced hypertension in male adult offspring, which prenatal metformin therapy prevented. The protective effects of prenatal metformin therapy on HFR/HFA-induced hypertension, including downregulation of the renin-angiotensin system, decrease in uric acid level, and reduction of oxidative stress. Our results highlighted that the programming effects of metformin administered prenatally might be different from those reported in adults, and that deserves further elucidation.

  16. Parental exposure to heavy fuel oil induces developmental toxicity in offspring of the sea urchin Strongylocentrotus intermedius.

    Science.gov (United States)

    Duan, Meina; Xiong, Deqi; Yang, Mengye; Xiong, Yijun; Ding, Guanghui

    2018-05-03

    The present study investigated the toxic effects of parental (maternal/paternal) exposure to heavy fuel oil (HFO) on the adult reproductive state, gamete quality and development of the offspring of the sea urchin Strongylocentrotus intermedius. Adult sea urchins were exposed to effluents from HFO-oiled gravel columns for 7 days to simulate an oil-contaminated gravel shore, and then gametes of adult sea urchins were used to produce embryos to determine developmental toxicity. For adult sea urchins, no significant difference in the somatic size and weight was found between the various oil loadings tested, while the gonad weight and gonad index were significantly decreased at higher oil loadings. The spawning ability of adults and fecundity of females significantly decreased. For gametes, no effect was observed on the egg size and fertilization success in any of the groups. However, a significant increase in the percentage of anomalies in the offspring was observed and then quantified by an integrative toxicity index (ITI) at 24 and 48 h post fertilization. The offspring from exposed parents showed higher ITI values with more malformed embryos. The results confirmed that parental exposure to HFO can cause adverse effects on the offspring and consequently affect the recruitment and population maintenance of sea urchins. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Lymphoma and lung cancer in offspring born to pregnant mice dosed with dibenzo[a,l]pyrene: The importance of in utero vs. lactational exposure

    International Nuclear Information System (INIS)

    Castro, David J.; Loehr, Christiane V.; Fischer, Kay A.; Pereira, Clifford B.; Williams, David E.

    2008-01-01

    The fetus and neonate cannot be viewed as 'little adults'; they are highly sensitive to toxicity from environmental chemicals. This phenomenon contributes to the fetal basis of adult disease. One example is transplacental carcinogenesis. Animal models demonstrate that environmental chemicals, to which pregnant women are daily exposed, can increase susceptibility of the offspring to cancer. It is uncertain to what degree in utero vs. lactational exposure contributes to cancer, especially for hydrophobic chemicals such as polyhalogenated biphenyls, ethers, dioxins, furans, etc., which can partition into breast milk. We developed a pregnant mouse model in which exposure to the polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), during late gestation, produces an aggressive T-cell lymphoma in offspring between 3 and 6 months of age. Survivors exhibit multiple lung and liver (males) tumors. Here, we adopt a cross-foster design with litters born to dams treated with DBP exchanged with those born to dams treated with vehicle. Exposure to DBP in utero (about 2 days) produced significantly greater mortality than residual DBP exposure only through breast milk (3 weeks of lactation). As previously observed pups in all groups with an ahr b-1/d ('responsive') genotype were more susceptible to lymphoma mortality than ahr d/d ('non-responsive') siblings. At termination of the study at 10 months, mice exposed in utero also had greater lung tumor multiplicity than mice exposed only during lactation. Our results demonstrate that short exposure to DBP during late gestation presents a greater risk to offspring than exposure to this very hydrophobic PAH following 3 weeks of nursing

  18. Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats

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    CAROLYNE D.S. SANTOS

    Full Text Available ABSTRACT Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT, Brown Adipose Tissue (BAT, and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation. After birth, only male offspring (F1 were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA. According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.

  19. The Influence of Parental Psychopathology on Offspring Suicidal Behavior across the Lifespan.

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    Geilson Lima Santana

    Full Text Available Suicide tends to occur in families, and parental psychopathology has been linked to offspring suicidal behaviors. This study explores the influence of parental mental disorders across the lifespan. Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional household study with a representative sample of the adult population living in the Sao Paulo Metropolitan Area, Brazil (N=2,942. Survival models examined bivariate and multivariate associations between a range of parental disorders and offspring suicidality. After controlling for comorbidity, number of mental disorders and offspring psychopathology, we found that parental psychopathology influences suicidal behaviors throughout most part of the life cycle, from childhood until young adult years. Generalized anxiety disorder (GAD and antisocial personality were associated with offspring suicidal ideation (OR 1.8 and 1.9, respectively, panic and GAD predicted suicidal attempts (OR 2.3 and 2.7, respectively, and panic was related to the transition from ideation to attempts (OR 2.7. Although noticed in many different stages of the lifespan, this influence is most evident during adolescence. In this period, depression and antisocial personality increased the odds of suicidal ideation (OR 5.1 and 3.2, respectively, and depression, panic disorder, GAD and substance abuse predicted suicidal attempts (OR varying from 1.7 to 3.8. In short, parental disorders characterized by impulsive-aggression and anxiety-agitation were the main predictors of offspring suicidality across the lifespan. This clinically relevant intergenerational transmission of suicide risk was independent of offspring mental disorders, and this underscores the need for a family approach to psychopathology.

  20. Effects of Offspring and Parental Inbreeding on Parent-Offspring Communication.

    Science.gov (United States)

    Mattey, Sarah N; Richardson, Jon; Ratz, Tom; Smiseth, Per T

    2018-06-01

    There is mounting evidence that inbreeding can have complex effects on social interactions among inbred and outbred individuals. Here, we investigate effects of offspring and maternal inbreeding on parent-offspring communication in the burying beetle Nicrophorus vespilloides. We find effects of the interaction between offspring and maternal inbreeding on maternal behavior. Outbred females provided more direct care toward inbred larvae, while inbred females provided similar levels of direct care toward inbred and outbred larvae. Furthermore, we find direct and indirect effects of offspring inbreeding on offspring begging and maternal behavior, respectively. Inbred larvae spent less time begging than outbred larvae, and (outbred) females provided more direct care and less indirect care toward inbred larvae. Finally, we find effects of the interaction between offspring and maternal inbreeding on larval body mass. Inbred and outbred offspring grew to a similar size when the female was outbred, while inbred offspring were of a smaller size when the female was inbred. Our results suggest that outbred females provided more care toward inbred offspring to compensate for their poor genetic quality. Our study advances our understanding of inbreeding by showing that inbreeding can have direct effects on the behavior of inbred individuals and indirect effects on the behavior of outbred individuals and that indirect effects on outbred individuals may in turn influence the fitness of inbred individuals.

  1. Low-functional programming of the CREB/BDNF/TrkB pathway mediates cognitive impairment in male offspring after prenatal dexamethasone exposure.

    Science.gov (United States)

    Dong, Wanting; Xu, Dan; Hu, Zewen; He, Xia; Guo, Zijing; Jiao, Zhexiao; Yu, Ying; Wang, Hui

    2018-02-01

    Adverse intrauterine environments can increase susceptibility to neuropsychiatric diseases that are related to cognitive impairment. In this study, we observed the cognitive impairment of male offspring rats after prenatal dexamethasone exposure (PDE) and explored the associated intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously injected with 0.2mg/kgd dexamethasone from gestational day 9 (GD9) to GD20. A cohort of the pregnant rat group was sacrificed on GD20, and the male fetal rats were collected. Another group of pregnant rats delivered their offspring naturally, and the male adult offspring rats were subjected to behavioural tests postnatally at 26 weeks and then sacrificed. The adult PDE male offspring rats exhibited cognitive impairment, decreased cell proliferation and increased cell apoptosis in the hippocampus, along with damaged synaptic plasticity and disrupted protein synthesis. Meanwhile, activation of GR and downregulation of the cAMP responsive element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin receptor tyrosine B (TrkB) signalling pathway were found in the adult PDE offspring rats. Further examinations indicated consistent alterations to the fetal hippocampus by PDE. We concluded that PDE can cause cognitive impairment in adult male offspring rats. The mechanism may be associated with low-functional programming of the hippocampal CREB/BDNF/TrkB signalling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity.

    Science.gov (United States)

    Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J

    2017-03-31

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues.

  3. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    Science.gov (United States)

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  4. Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.

    Science.gov (United States)

    Owuor, Theresa O; Reid, Michaela; Reschke, Lauren; Hagemann, Ian; Greco, Suellen; Modi, Zeel; Moley, Kelle H

    2018-01-01

    Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES.

  5. Do Parental Stressors and Avoidance Coping Mediate between Parental Depression and Offspring Depression? A 23-Year Follow-Up

    Science.gov (United States)

    Timko, Christine; Cronkite, Ruth C.; Moos, Rudolf H.

    2010-01-01

    We examined whether parents' stressors and avoidance coping when offspring were children helped to explain associations between parent depression at baseline and offspring's avoidance coping and depression in adulthood. Self-report data were collected at baseline and 1 year from parents (N = 326) and at 23 years from adult offspring (N = 326).…

  6. Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study.

    Science.gov (United States)

    Han, T S; Hart, C L; Haig, C; Logue, J; Upton, M N; Watt, G C M; Lean, M E J

    2015-11-02

    Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. Cross-sectional general population survey. Scotland. 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45-64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30-59 years surveyed in 1996. Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. Regression coefficients for BMI associations between father-son (0.30) and mother-daughter (0.33) were greater than father-daughter (0.23) or mother-son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (pparental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. There are modest genetic/epigenetic influences on the environmental factors behind adverse adiposity. Maternal smoking appears a specific hazard on obesity and metabolic

  7. Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

    Directory of Open Access Journals (Sweden)

    María Teresa Ramírez-López

    Full Text Available Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS. In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a the adult expression of endocannabinoid-related behaviors, b the metabolic profile of adult offspring and c the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

  8. A test of maternal programming of offspring stress response to predation risk in threespine sticklebacks.

    Science.gov (United States)

    Mommer, Brett C; Bell, Alison M

    2013-10-02

    Non-genetic maternal effects are widespread across taxa and challenge our traditional understanding of inheritance. Maternal experience with predators, for example, can have lifelong consequences for offspring traits, including fitness. Previous work in threespine sticklebacks showed that females exposed to simulated predation risk produced eggs with higher cortisol content and offspring with altered anti-predator behavior. However, it is unknown whether this maternal effect is mediated via the offspring glucocorticoid stress response and if it is retained over the entire lifetime of offspring. Therefore, we tested the hypothesis that maternal exposure to simulated predation risk has long-lasting effects on the cortisol response to simulated predation risk in stickleback offspring. We measured circulating concentrations of cortisol before (baseline), 15 min after, and 60 min after exposure to a simulated predation risk. We compared adult offspring of predator-exposed mothers and control mothers in two different social environments (alone or in a group). Relative to baseline, offspring plasma cortisol was highest 15 min after exposure to simulated predation risk and decreased after 60 min. Offspring of predator-exposed mothers differed in the cortisol response to simulated predation risk compared to offspring of control mothers. In general, females had higher cortisol than males, and fish in a group had lower cortisol than fish that were by themselves. The buffering effect of the social environment did not differ between maternal treatments or between males and females. Altogether the results show that while a mother's experience with simulated predation risk might affect the physiological response of her adult offspring to a predator, sex and social isolation have much larger effects on the stress response to predation risk in sticklebacks. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Antenatal hypoxia induces programming of reduced arterial blood pressure response in female rat offspring: role of ovarian function.

    Directory of Open Access Journals (Sweden)

    DaLiao Xiao

    Full Text Available In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring.

  10. Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle

    2016-01-01

    High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compa......, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension.......High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We...... compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents...

  11. Gluten-Free Diet Only during Pregnancy Efficiently Prevents Diabetes in NOD Mouse Offspring

    DEFF Research Database (Denmark)

    Antvorskov, Julie C; Josefsen, Knud; Haupt-Jorgensen, Martin

    2016-01-01

    Studies have documented that the pathogenesis of autoimmune diabetes is influenced by the intake of gluten. Aims. To investigate the importance of gluten exposure during pregnancy and the subsequent development of autoimmune diabetes in offspring. Methods. Nonobese diabetic mice were divided into...

  12. Squamate hatchling size and the evolutionary causes of negative offspring size allometry.

    Science.gov (United States)

    Meiri, S; Feldman, A; Kratochvíl, L

    2015-02-01

    Although fecundity selection is ubiquitous, in an overwhelming majority of animal lineages, small species produce smaller number of offspring per clutch. In this context, egg, hatchling and neonate sizes are absolutely larger, but smaller relative to adult body size in larger species. The evolutionary causes of this widespread phenomenon are not fully explored. The negative offspring size allometry can result from processes limiting maximal egg/offspring size forcing larger species to produce relatively smaller offspring ('upper limit'), or from a limit on minimal egg/offspring size forcing smaller species to produce relatively larger offspring ('lower limit'). Several reptile lineages have invariant clutch sizes, where females always lay either one or two eggs per clutch. These lineages offer an interesting perspective on the general evolutionary forces driving negative offspring size allometry, because an important selective factor, fecundity selection in a single clutch, is eliminated here. Under the upper limit hypotheses, large offspring should be selected against in lineages with invariant clutch sizes as well, and these lineages should therefore exhibit the same, or shallower, offspring size allometry as lineages with variable clutch size. On the other hand, the lower limit hypotheses would allow lineages with invariant clutch sizes to have steeper offspring size allometries. Using an extensive data set on the hatchling and female sizes of > 1800 species of squamates, we document that negative offspring size allometry is widespread in lizards and snakes with variable clutch sizes and that some lineages with invariant clutch sizes have unusually steep offspring size allometries. These findings suggest that the negative offspring size allometry is driven by a constraint on minimal offspring size, which scales with a negative allometry. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary

  13. Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal, family study

    Science.gov (United States)

    MacGregor, Erica K.; Grunebaum, Michael F.; Galfalvy, Hanga C.; Melhem, Nadine; Burke, Ainsley K.; Brent, David A.; Oquendo, Maria A.; Mann, J. John

    2015-01-01

    Objective To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. Method 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992–2008 during a longitudinal family study completed January 31, 2014. Results Parent avoidant attachment predicted offspring suicide attempts at a trend level (p=0.083). Parent anxious attachment did not predict offspring attempts (p=0.961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (p=0.034), and in offspring suicide attempters, was associated with greater intent (p=0.045) and lethality of attempts (p=0.003). Avoidant attachment in parents was associated with offspring impulsivity (p=0.025) and major depressive disorder (p=0.012). Parent avoidant attachment predicted a greater number of suicide attempts (p=0.048) and greater intent in offspring attempters (p=0.003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Conclusion Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parent attachment traits were associated with impulsivity and major depressive disorder in all offspring, and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. PMID:25098943

  14. Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal family study.

    Science.gov (United States)

    MacGregor, Erica K; Grunebaum, Michael F; Galfalvy, Hanga C; Melhem, Nadine; Burke, Ainsley K; Brent, David A; Oquendo, Maria A; Mann, J John

    2014-08-01

    To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992-2008 during a longitudinal family study completed January 31, 2014. Parental avoidant attachment predicted offspring suicide attempts at a trend level (P = .083). Parental anxious attachment did not predict offspring attempts (P = .961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (P = .034) and, in offspring suicide attempters, was associated with greater intent (P = .045) and lethality of attempts (P = .003). Avoidant attachment in parents was associated with offspring impulsivity (P = .025) and major depressive disorder (P = .012). Parental avoidant attachment predicted a greater number of suicide attempts (P = .048) and greater intent in offspring attempters (P = .003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parental attachment traits were associated with impulsivity and major depressive disorder in all offspring and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. © Copyright 2014 Physicians Postgraduate Press, Inc.

  15. Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring.

    Science.gov (United States)

    Canetta, Sarah E; Bao, Yuanyuan; Co, Mary Dawn T; Ennis, Francis A; Cruz, John; Terajima, Masanori; Shen, Ling; Kellendonk, Christoph; Schaefer, Catherine A; Brown, Alan S

    2014-05-01

    The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features. The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay. No association was observed between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serological influenza exposure was related to a significant fivefold greater risk of bipolar disorder with psychotic features. The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, these results may suggest that prenatal influenza is a risk factor for psychosis rather than for a specific psychotic disorder diagnosis.

  16. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    Directory of Open Access Journals (Sweden)

    You-Lin eTain

    2015-12-01

    Full Text Available Prenatal dexamethasone (DEX exposure and high-fat (HF intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS, to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification.

  17. Methylation changes of H19 gene in sperms of X-irradiated mouse and maintenance in offspring

    International Nuclear Information System (INIS)

    Zhu Bin; Huang Xinghua; Chen Jindong; Lu Yachao; Chen Ying; Zhao Jingyong

    2006-01-01

    The nature of imprinting is just differential methylation of imprinted genes. Unlike the non-imprinted genes, the methylation pattern of imprinted genes established during the period of gametogenesis remains unchangeable after fertilization and during embryo development. It implies that gametogenesis is the key stage for methylation pattern of imprinted genes. The imprinting interfered by exogenous factors during this stage could be inherited to offspring and cause genetic effect. Now many studies have proved that ionizing irradiation could disturb DNA methylation. Here we choose BALB/c mice as a research model and X-ray as interfering source to further clarify it. We discovered that the whole-body irradiation of X-ray to male BALB/c mice could influence the methylation pattern of H 19 gene in sperms, which resulted in some cytosines of partial CpG islands in the imprinting control region could not transform to methylated cytosines. Furthermore, by copulating the interfered male mice with normal female, we analyzed the promoter methylation pattern of H 19 in offspring fetal liver and compared the same to the pattern of male parent in sperms. We found that the majority of methylation changes in offspring liver were related to the ones in their parent sperms. Our data proved that the changes of the H 19 gene methylation pattern interfered by X-ray irradiation could be transmitted and maintained in First-generation offspring

  18. Self-esteem and depression: ten year follow-up of mothers and offspring.

    Science.gov (United States)

    Miller, L; Warner, V; Wickramaratne, P; Weissman, M

    1999-01-01

    The association between maternal bonding style, offspring low self-esteem and offspring depression status was assessed by maternal depression status. Sixty mothers and 137 offspring were independently assessed over the course of a ten year follow-up study. Assessments included the Schedule for Affective Disorders and Schizophrenia (SADS-LA), Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS), the Coopersmith Self-Esteem Inventory (CSEI) and the Parental Bonding Instrument (PBI). Among daughters of mothers with a history of depression, maternal affectionless-control was associated with daughter low self-esteem which was associated with daughter depression at ten year follow-up. Among daughters of mothers without a history of depression, maternal affectionless-control was not associated with daughter low self-esteem, which was not associated with daughter depression at ten year follow-up but which was associated with a history of childhood depression. None of these associations were found to be significant among sons. As self-esteem was not measured at ten year follow-up, among offspring the stability of self-esteem could not be assessed, nor could the association between adult self-esteem and adult depression. Clinical presentation of low self-esteem in girls should be assessed in the context of maternal depression status.

  19. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

    Science.gov (United States)

    Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

    2017-01-16

    Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. As expected, adult offspring fed the S diet post weaning became obese (body weight: Peffect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

  20. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    Science.gov (United States)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  1. Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

    DEFF Research Database (Denmark)

    Kimura, Masayuki; Cherkas, Lynn F; Kato, Bernet S

    2008-01-01

    ), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (50 years) donors. Paternal age...... had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice......Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different...

  2. Programming of mouse obesity by maternal exposure to concentrated ambient fine particles.

    Science.gov (United States)

    Chen, Minjie; Wang, Xiaoke; Hu, Ziying; Zhou, Huifen; Xu, Yanyi; Qiu, Lianglin; Qin, Xiaobo; Zhang, Yuhao; Ying, Zhekang

    2017-06-23

    Many diseases including obesity may originate through alterations in the early-life environment that interrupts fetal development. Increasing evidence has shown that exposure to ambient fine particles (PM 2.5 ) is associated with abnormal fetal development. However, its long-term metabolic effects on offspring have not been systematically investigated. To determine if maternal exposure to PM 2.5 programs offspring obesity, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) during pre-conception, pregnancy, and lactation, and the developmental and metabolic responses of offspring were assessed. The growth trajectory of offspring revealed that maternal exposure to CAP significantly decreased offspring birth weight but increased body weight of adult male but not female offspring, and the latter was expressed as increased adiposity. These adult male offspring had increased food intake, but were sensitive to exogenous leptin. Their hypothalamic expression of Socs3 and Pomc, two target genes of leptin, was not changed, and the hypothalamic expression of NPY, an orexigenic peptide that is inhibited by leptin, was significantly increased. These decreases in central anorexigenic signaling were accompanied by reduced plasma leptin and its expression in adipose tissues, the primary source of circulating leptin. In contrast, maternal exposure did not significantly change any of these indexes in adult female offspring. Pyrosequencing demonstrated that the leptin promoter methylation of adipocytes was significantly increased in CAP-exposed male but not female offspring. Our data indicate that maternal exposure to ambient PM 2.5 programs obesity in male offspring probably through alterations in the methylation of the promoter region of the leptin gene.

  3. Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.

    Science.gov (United States)

    Rajan, T V; Bailis, J M; Yates, J A; Shultz, L D; Greiner, D L; Nelson, F K

    1994-12-01

    We have used the severe combined immunodeficient C.B-17-scid/scid mouse to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infection with the human filarial parasite, Brugia malayi. C.B-17-scid/scid mice are permissive for infection while immunocompetent C.B-17(-)+/+ mice are uniformly resistant. Reciprocal matings of C.B-17-scid/scid and C.B-17(-)+/+ mice were performed. The C.B-17-scid/scid females were either naive or infected with Brugia malayi. The resulting immunocompetent C.B-17-scid/+ and C.B-17(-)+/scid progeny were challenged at weaning with an intraperitoneal injection of Brugia malayi third stage larvae known to produce patent infection in > 95% of C.B-17-scid/scid mice. We observed that 40.0%l (34/85) of the immunocompetent offspring of C.B-17-scid/scid females x C.B-17(-)+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was observed in susceptibility to infection between the progeny of infected or uninfected C.B-17-scid/scid mothers mated with C.B-17(-)+/+ fathers, arguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous progeny of wild type C.B-17(-)+/+ females mated with C.B-17-scid/scid males were permissive. These observations document conversion of a 'resistant' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offspring susceptibility to infection with Brugia malayi.

  4. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.

    Directory of Open Access Journals (Sweden)

    Angelica B Bernal

    Full Text Available BACKGROUND: We have shown recently that maternal undernutrition (UN advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of

  5. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

  6. Offspring of prenatal IV nicotine exposure exhibit increased sensitivity to the reinforcing effects of methamphetamine

    Directory of Open Access Journals (Sweden)

    Steven Brown Harrod

    2012-06-01

    Full Text Available Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH in offspring using a low dose, intravenous (IV exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection or prenatal saline (PS 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1 or METH-induced conditioned taste aversion (CTA; experiment 2 procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/injection; fixed-ratio 3 and they were tested on varying doses the reinforcer (0.0005-1.0 mg/kg/injection. For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc followed by fourteen daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal’s curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that adult offspring of IV PN exposure exhibited altered motivation for the reinforcing effects of METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

  7. An adult passive transfer mouse model to study desmoglein 3 signaling in pemphigus vulgaris.

    Science.gov (United States)

    Schulze, Katja; Galichet, Arnaud; Sayar, Beyza S; Scothern, Anthea; Howald, Denise; Zymann, Hillard; Siffert, Myriam; Zenhäusern, Denise; Bolli, Reinhard; Koch, Peter J; Garrod, David; Suter, Maja M; Müller, Eliane J

    2012-02-01

    Evidence has accumulated that changes in intracellular signaling downstream of desmoglein 3 (Dsg3) may have a significant role in epithelial blistering in the autoimmune disease pemphigus vulgaris (PV). Currently, most studies on PV involve passive transfer of pathogenic antibodies into neonatal mice that have not finalized epidermal morphogenesis, and do not permit analysis of mature hair follicles (HFs) and stem cell niches. To investigate Dsg3 antibody-induced signaling in the adult epidermis at defined stages of the HF cycle, we developed a model with passive transfer of AK23 (a mouse monoclonal pathogenic anti-Dsg3 antibody) into adult 8-week-old C57Bl/6J mice. Validated using histopathological and molecular methods, we found that this model faithfully recapitulates major features described in PV patients and PV models. Two hours after AK23 transfer, we observed widening of intercellular spaces between desmosomes and EGFR activation, followed by increased Myc expression and epidermal hyperproliferation, desmosomal Dsg3 depletion, and predominant blistering in HFs and oral mucosa. These data confirm that the adult passive transfer mouse model is ideally suited for detailed studies of Dsg3 antibody-mediated signaling in adult skin, providing the basis for investigations on novel keratinocyte-specific therapeutic strategies.

  8. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

    Directory of Open Access Journals (Sweden)

    Jack W Hickmott

    2016-01-01

    Full Text Available Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6 gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

  9. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina.

    Science.gov (United States)

    Hickmott, Jack W; Chen, Chih-Yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

    2016-01-01

    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

  10. As-resistance in laboratory-reared F1, F2 and F3 generation offspring of the earthworm Lumbricus rubellus inhabiting an As-contaminated mine soil

    Energy Technology Data Exchange (ETDEWEB)

    Langdon, C.J., E-mail: clangdon1@btinternet.co [C/O The Open University in the North, Baltic Buiness Quarter, Abbots Hill, Gateshead NE8 3DF (United Kingdom); Morgan, A.J., E-mail: morganaj1@cardiff.ac.u [Cardiff School of Biosciences, Cardiff University, P.O. Box 913, Cardiff CF11 3TL, Wales (United Kingdom); Charnock, J.M., E-mail: john.charnock@manchester.ac.u [STFC Daresbury Laboratory, Warrington, Cheshire WA4 4AD (United Kingdom); School of Earth, Atmospheric and Environmental Sciences, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Semple, K.T., E-mail: k.semple@lancaster.ac.u [Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom); Lowe, C.N., E-mail: cnlowe@uclan.ac.u [School of Built and Natural Environment, University of Central Lancashire, Preston PR1 2HE (United Kingdom)

    2009-11-15

    Previous studies provided no unequivocal evidence demonstrating that field populations of Lumbricus rubellus Hoffmeister (1843), exhibit genetically inherited resistance to As-toxicity. In this study F1, F2 and F3 generation offspring derived from adults inhabiting As-contaminated field soil were resistant when exposed to 2000 mg kg{sup -1} sodium arsenate. The offspring of uncontaminated adults were not As-resistant. Cocoon viability was 80% for F1 and 82% for F2 offspring from As-contaminated adults and 59% in the F1 control population. High energy synchrotron analysis was used to determine whether ligand complexation of As differed in samples of: resistant mine-site adults, the resistant F1 and F2 offspring of the mine-site earthworms exposed to the LC{sub 25} sodium arsenate (700 mg kg{sup -1}) of the F1 parental generation; and adult L. rubellus from an uncontaminated site exposed to LC{sub 25} concentrations of sodium arsenate (50 mg kg{sup -1}). XANES and EXAFS indicated that As was present as a sulfur-coordinated species. - As-resistance in F1, F2 and F3 offspring of the earthworm Lumbricus rubellus.

  11. As-resistance in laboratory-reared F1, F2 and F3 generation offspring of the earthworm Lumbricus rubellus inhabiting an As-contaminated mine soil

    International Nuclear Information System (INIS)

    Langdon, C.J.; Morgan, A.J.; Charnock, J.M.; Semple, K.T.; Lowe, C.N.

    2009-01-01

    Previous studies provided no unequivocal evidence demonstrating that field populations of Lumbricus rubellus Hoffmeister (1843), exhibit genetically inherited resistance to As-toxicity. In this study F1, F2 and F3 generation offspring derived from adults inhabiting As-contaminated field soil were resistant when exposed to 2000 mg kg -1 sodium arsenate. The offspring of uncontaminated adults were not As-resistant. Cocoon viability was 80% for F1 and 82% for F2 offspring from As-contaminated adults and 59% in the F1 control population. High energy synchrotron analysis was used to determine whether ligand complexation of As differed in samples of: resistant mine-site adults, the resistant F1 and F2 offspring of the mine-site earthworms exposed to the LC 25 sodium arsenate (700 mg kg -1 ) of the F1 parental generation; and adult L. rubellus from an uncontaminated site exposed to LC 25 concentrations of sodium arsenate (50 mg kg -1 ). XANES and EXAFS indicated that As was present as a sulfur-coordinated species. - As-resistance in F1, F2 and F3 offspring of the earthworm Lumbricus rubellus.

  12. Maternal modulation of paternal effects on offspring development.

    Science.gov (United States)

    Mashoodh, Rahia; Habrylo, Ireneusz B; Gudsnuk, Kathryn M; Pelle, Geralyn; Champagne, Frances A

    2018-03-14

    The paternal transmission of environmentally induced phenotypes across generations has been reported to occur following a number of qualitatively different exposures and appear to be driven, at least in part, by epigenetic factors that are inherited via the sperm. However, previous studies of paternal germline transmission have not addressed the role of mothers in the propagation of paternal effects to offspring. We hypothesized that paternal exposure to nutritional restriction would impact male mate quality and subsequent maternal reproductive investment with consequences for the transmission of paternal germline effects. In the current report, using embryo transfer in mice, we demonstrate that sperm factors in adult food restricted males can influence growth rate, hypothalamic gene expression and behaviour in female offspring. However, under natural mating conditions females mated with food restricted males show increased pre- and postnatal care, and phenotypic outcomes observed during embryo transfer conditions are absent or reversed. We demonstrate that these compensatory changes in maternal investment are associated with a reduced mate preference for food restricted males and elevated gene expression within the maternal hypothalamus. Therefore, paternal experience can influence offspring development via germline inheritance, but mothers can serve as a modulating factor in determining the impact of paternal influences on offspring development. © 2018 The Author(s).

  13. Development of a nematode offspring counting assay for rapid and simple soil toxicity assessment.

    Science.gov (United States)

    Kim, Shin Woong; Moon, Jongmin; Jeong, Seung-Woo; An, Youn-Joo

    2018-05-01

    Since the introduction of standardized nematode toxicity assays by the American Society for Testing and Materials (ASTM) and International Organization for Standardization (ISO), many studies have reported their use. Given that the currently used standardized nematode toxicity assays have certain limitations, in this study, we examined the use of a novel nematode offspring counting assay for evaluating soil ecotoxicity based on a previous soil-agar isolation method used to recover live adult nematodes. In this new assay, adult Caenorhabditis elegans were exposed to soil using a standardized toxicity assay procedure, and the resulting offspring in test soils attracted by a microbial food source in agar plates were counted. This method differs from previously used assays in terms of its endpoint, namely, the number of nematode offspring. The applicability of the bioassay was demonstrated using metal-spiked soils, which revealed metal concentration-dependent responses, and with 36 field soil samples characterized by different physicochemical properties and containing various metals. Principal component analysis revealed that texture fraction (clay, sand, and silt) and electrical conductivity values were the main factors influencing the nematode offspring counting assay, and these findings warrant further investigation. The nematode offspring counting assay is a rapid and simple process that can provide multi-directional toxicity assessment when used in conjunction with other standard methods. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Chronic schistosomiasis during pregnancy epigenetically reprograms T-cell differentiation in offspring of infected mothers.

    Science.gov (United States)

    Klar, Kathrin; Perchermeier, Sophie; Bhattacharjee, Sonakshi; Harb, Hani; Adler, Thure; Istvanffy, Rouzanna; Loffredo-Verde, Eva; Oostendorp, Robert A; Renz, Harald; Prazeres da Costa, Clarissa

    2017-05-01

    Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B-cell and T-cell development. Therefore, we focused our analyses on T-cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into T H 1 cells, whereas T H 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T-cell compartment affecting T H 2 and T H 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T-cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging in Offspring of Holocaust Survivors

    Science.gov (United States)

    Shrira, Amit; Ayalon, Liat; Bensimon, Moshe; Bodner, Ehud; Rosenbloom, Tova; Yadid, Gal

    2017-01-01

    A fascinating, yet underexplored, question is whether traumatic events experienced by previous generations affect the aging process of subsequent generations. This question is especially relevant for offspring of Holocaust survivors (OHS), who begin to face the aging process. Some preliminary findings point to greater physical dysfunction among middle-aged OHS, yet the mechanisms behind this dysfunction need further clarification. Therefore, the current studies assess aging OHS using the broad-scoped conceptualization of successful aging, while examining whether offspring successful aging relates to parental post-traumatic stress disorder (PTSD) symptoms and offspring’s secondary traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31) completed measures of parental PTSD, secondary traumatization, as well as successful aging indices – objective (medical conditions, disability and somatic symptoms) and subjective (perceptions of one’s aging). Relative to comparisons and OHS who reported that none of their parents suffered from probable PTSD, OHS who reported that their parents suffered from probable PTSD had lower scores in objective and subjective measures of successful aging. Mediation analyses showed that higher level of secondary traumatization mediated the relationship between parental PTSD and less successful aging in the offspring. Study 2 included 154 dyads of parents (mean age = 81.86) and their adult offspring (mean age = 54.48). Parents reported PTSD symptoms and offspring reported secondary traumatization and completed measures of objective successful aging. Relative to comparisons, OHS whose parent had probable PTSD have aged less successfully. Once again, offspring secondary traumatization mediated the effect. The findings suggest that parental post-traumatic reactions assessed both by offspring (Study 1) and by parents themselves (Study 2) take part in shaping the aging of the subsequent generation via reactions of secondary

  16. Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging in Offspring of Holocaust Survivors

    Directory of Open Access Journals (Sweden)

    Amit Shrira

    2017-06-01

    Full Text Available A fascinating, yet underexplored, question is whether traumatic events experienced by previous generations affect the aging process of subsequent generations. This question is especially relevant for offspring of Holocaust survivors (OHS, who begin to face the aging process. Some preliminary findings point to greater physical dysfunction among middle-aged OHS, yet the mechanisms behind this dysfunction need further clarification. Therefore, the current studies assess aging OHS using the broad-scoped conceptualization of successful aging, while examining whether offspring successful aging relates to parental post-traumatic stress disorder (PTSD symptoms and offspring’s secondary traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31 completed measures of parental PTSD, secondary traumatization, as well as successful aging indices – objective (medical conditions, disability and somatic symptoms and subjective (perceptions of one’s aging. Relative to comparisons and OHS who reported that none of their parents suffered from probable PTSD, OHS who reported that their parents suffered from probable PTSD had lower scores in objective and subjective measures of successful aging. Mediation analyses showed that higher level of secondary traumatization mediated the relationship between parental PTSD and less successful aging in the offspring. Study 2 included 154 dyads of parents (mean age = 81.86 and their adult offspring (mean age = 54.48. Parents reported PTSD symptoms and offspring reported secondary traumatization and completed measures of objective successful aging. Relative to comparisons, OHS whose parent had probable PTSD have aged less successfully. Once again, offspring secondary traumatization mediated the effect. The findings suggest that parental post-traumatic reactions assessed both by offspring (Study 1 and by parents themselves (Study 2 take part in shaping the aging of the subsequent generation via reactions of

  17. Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

    Energy Technology Data Exchange (ETDEWEB)

    Martinez–Arguelles, D.B. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); McIntosh, M.; Rohlicek, C.V. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Pediatrics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Culty, M. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Zirkin, B.R. [Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Papadopoulos, V., E-mail: vassilios.papadopoulos@mcgill.ca [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States)

    2013-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

  18. Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

    Science.gov (United States)

    Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

    2013-01-01

    An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

  19. Maternal high-fat diet accelerates development of Crohn's disease-like ileitis in TNF ΔaRE/WT offspring

    NARCIS (Netherlands)

    Gruber, Lisa; Hemmerling, Jana; Schüppel, Valentina; Müller, Michael; Boekschoten, M.V.; Haller, Dirk

    2015-01-01

    Background: Maternal high-fat diet (HFD) and obesity increases the risk of the offspring to develop inflammatory processes in various organs including the gut. We hypothesized that maternal diet-induced obesity programs the fetal gut towards inflammation in a mouse model of genetically-driven

  20. A maternal "junk-food" diet reduces sensitivity to the opioid antagonist naloxone in offspring postweaning.

    Science.gov (United States)

    Gugusheff, Jessica R; Ong, Zhi Yi; Muhlhausler, Beverly S

    2013-03-01

    Perinatal exposure to a maternal "junk-food" diet has been demonstrated to increase the preference for palatable diets in adult offspring. We aimed to determine whether this increased preference could be attributed to changes in μ-opioid receptor expression within the mesolimbic reward pathway. We report here that mRNA expression of the μ-opioid receptor in the ventral tegmental area (VTA) at weaning was 1.4-fold (males) and 1.9-fold (females) lower in offspring of junk-food (JF)-fed rat dams than in offspring of dams fed a standard rodent diet (control) (Pjunk-food diet results in early desensitization of the opioid system which may explain the increased preference for junk food in these offspring.

  1. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

    Science.gov (United States)

    Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

    2016-11-01

    Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

  2. The Association of Maternal Socialization in Childhood and Adolescence with Adult Offsprings' Sympathy/Caring

    Science.gov (United States)

    Eisenberg, Nancy; VanSchyndel, Sarah K.; Hofer, Claire

    2015-01-01

    The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood…

  3. Doublecortin-like knockdown in the adult mouse brain : implications for neurogenesis, neuroplasticity and behaviour

    NARCIS (Netherlands)

    Saaltink, Dirk-Jan

    2014-01-01

    The results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons (hippocampus and olfactory forebrain), DCL expression was found in three novel brain areas namely

  4. When parents disclose BRCA1/2 test results: their communication and perceptions of offspring response.

    Science.gov (United States)

    Bradbury, Angela R; Patrick-Miller, Linda; Egleston, Brian L; Olopade, Olufunmilayo I; Daly, Mary B; Moore, Cynthia W; Sands, Colleen B; Schmidheiser, Helen; Kondamudi, Preethi K; Feigon, Maia; Ibe, Comfort N; Daugherty, Christopher K

    2012-07-01

    BRCA1/2 testing is not recommended for children, as risk reduction measures and screening are not generally recommended before 25 years old (YO). Little is known about the prevalence and predictors of parent communication to offspring and how offspring respond to this communication. Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least 1 child parents completed interviews (61% response rate), reporting on 505 offspring. Twenty-nine percent of parents were BRCA1/2 mutation carriers. Three hundred thirty-four (66%) offspring learned of their parent's test result. Older offspring age (P ≤ .01), offspring gender (female, P = .05), parents' negative test result (P = .03), and parents' education (high school only, P = .02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). Thirteen percent of offspring were reported to experience concern or distress (11%) in response to parental communication of their test results. Distress was more frequently perceived among offspring learning of their parent's BRCA1/2 positive or variant of uncertain significance result. Many parents communicate their BRCA1/2 test results to young offspring. Parents' perceptions of offspring responses appear to vary by offspring age and parent test result. A better understanding of how young offspring respond to information about hereditary risk for adult cancer could provide opportunities to optimize adaptive psychosocial responses to risk information and performance of health behaviors, in adolescence and throughout an at-risk life span. Copyright © 2012 American Cancer Society.

  5. Targeted disruption of the mouse Lipoma Preferred Partner gene

    International Nuclear Information System (INIS)

    Vervenne, Hilke B.V.K.; Crombez, Koen R.M.O.; Delvaux, Els L.; Janssens, Veerle; Ven, Wim J.M. van de; Petit, Marleen M.R.

    2009-01-01

    LPP (Lipoma Preferred Partner) is a zyxin-related cell adhesion protein that is involved in the regulation of cell migration. We generated mice with a targeted disruption of the Lpp gene and analysed the importance of Lpp for embryonic development and adult functions. Aberrant Mendelian inheritance in heterozygous crosses suggested partial embryonic lethality of Lpp -/- females. Fertility of Lpp -/- males was proven to be normal, however, females from Lpp -/- x Lpp -/- crosses produced a strongly reduced number of offspring, probably due to a combination of female embryonic lethality and aberrant pregnancies. Apart from these developmental and reproductive abnormalities, Lpp -/- mice that were born reached adulthood without displaying any additional macroscopic defects. On the other hand, Lpp -/- mouse embryonic fibroblasts exhibited reduced migration capacity, reduced viability, and reduced expression of some Lpp interaction partners. Finally, we discovered a short nuclear form of Lpp, expressed mainly in testis via an alternative promoter.

  6. Female Offspring From Chronic Hyperandrogenemic Dams Exhibit Delayed Puberty and Impaired Ovarian Reserve.

    Science.gov (United States)

    Wang, Zhiqiang; Shen, Mingjie; Xue, Ping; DiVall, Sara A; Segars, James; Wu, Sheng

    2018-02-01

    Female offspring of many species exposed to high doses of androgens in utero experience endocrine dysfunction during adulthood. The phenotype of offspring from females with prepregnancy hyperandrogenemia and impaired ovulation, however, has not been examined. We developed a mouse model of hyperandrogenemia by implanting a low-dose dihydrotestosterone (DHT) pellet 15 days before conception. Female offspring born to dams with hyperandrogenemia (DHT daughters) had delayed puberty (P DHT (non-DHT daughters, PND37.5). Serum follicle-stimulating hormone (FSH) levels in the DHT daughters were fourfold higher (P DHT daughters (controls). DHT daughters showed an extended time in metestrus/diestrus and a shorter time in the proestrus/estrus phase compared with non-DHT daughters (P DHT daughters compared with non-DHT daughters (P DHT daughters compared with non-DHT daughters. Daughters from hyperandrogenemic females exhibited elevated prepubertal FSH levels, diminished ovarian response to superovulation, impaired estrous cyclicity, delayed onset of puberty, and reduced ovarian reserve, suggesting that fetal androgen exposure had lasting effects on female reproductive function. Copyright © 2018 Endocrine Society.

  7. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    Science.gov (United States)

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

  8. The effect of maternal chromium status on lipid metabolism in female elderly mice offspring and involved molecular mechanism.

    Science.gov (United States)

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-04-30

    Maternal malnutrition leads to the incidence of metabolic diseases in offspring. The purpose of this project was to examine whether maternal low chromium could disturb normal lipid metabolism in offspring, altering adipose cell differentiation and leading to the incidence of lipid metabolism diseases, including metabolic syndrome and obesity. Female C57BL mice were given a control diet (CD) or a low chromium diet (LCD) during the gestational and lactation periods. After weaning, offspring was fed with CD or LCD. The female offspring were assessed at 32 weeks of age. Fresh adipose samples from CD-CD group and LCD-CD group were collected. Genome mRNA were analysed using Affymetrix GeneChip Mouse Gene 2.0 ST Whole Transcript-based array. Differentially expressed genes (DEGs) were analysed based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis database. Maternal low chromium irreversibly increased offspring body weight, fat-pad weight, serum triglyceride (TG) and TNF-α. Eighty five genes increased and 109 genes reduced in the offspring adipose of the maternal low chromium group. According to KEGG pathway and String analyses, the PPAR signalling pathway may be the key controlled pathway related to the effect of maternal low chromium on female offspring. Maternal chromium status have long-term effects of lipid metabolism in female mice offspring. Normalizing offspring diet can not reverse these effects. The potential underlying mechanisms are the disturbance of the PPAR signalling pathway in adipose tissue. © 2017 The Author(s).

  9. Egg size and offspring quality: a meta-analysis in birds.

    Science.gov (United States)

    Krist, Miloš

    2011-08-01

    Parents affect offspring fitness by propagule size and quality, selection of oviposition site, quality of incubation, feeding of dependent young, and their defence against predators and parasites. Despite many case studies on each of these topics, this knowledge has not been rigorously integrated into individual parental care traits for any taxon. Consequently, we lack a comprehensive, quantitative assessment of how parental care modifies offspring phenotypes. This meta-analysis of 283 studies with 1805 correlations between egg size and offspring quality in birds is intended to fill this gap. The large sample size enabled testing of how the magnitude of the relationship between egg size and offspring quality depends on a number of variables. Egg size was positively related to nearly all studied offspring traits across all stages of the offspring life cycle. Not surprisingly, the relationship was strongest at hatching but persisted until the post-fledging stage. Morphological traits were the most closely related to egg size but significant relationships were also found with hatching success, chick survival, and growth rate. Non-significant effect sizes were found for egg fertility, chick immunity, behaviour, and life-history or sexual traits. Effect size did not depend on whether chicks were raised by their natural parents or were cross-fostered to other territories. Effect size did not depend on species-specific traits such as developmental mode, clutch size, and relative size of the egg, but was larger if tested in captive compared to wild populations and between rather than within broods. In sum, published studies support the view that egg size affects juvenile survival. There are very few studies that tested the relationship between egg size and the fecundity component of offspring fitness, and no studies on offspring survival as adults or on global fitness. More data are also needed for the relationships between egg size and offspring behavioural and

  10. The Effect of Parents' Attitudes toward Divorce on Offspring's Attitudes: Gender and Parental Divorce as Mediating Factors

    Science.gov (United States)

    Kapinus, Carolyn A.

    2004-01-01

    This study addresses three questions: (a) What influence do parents' attitudes toward divorce have on offspring's attitudes? (b) How are offspring's attitudes toward divorce influenced by parental divorce, and do the effects vary depending on the gender of the child? and (c) How do conditions surrounding parental divorce influence young adults'…

  11. The perfect host: a mouse host embryo facilitating more efficient germ line transmission of genetically modified embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Robert A Taft

    Full Text Available There is a continual need to improve efficiency in creating precise genetic modifications in mice using embryonic stem cells (ESCs. We describe a novel approach resulting in 100% germline transmission from competent injected ESCs. We developed an F1 mouse host embryo (Perfect Host, PH that selectively ablates its own germ cells via tissue-specific induction of diphtheria toxin. This approach allows competent microinjected ESCs to fully dominate the germline, eliminating competition for this critical niche in the developing and adult animal. This is in contrast to conventional methods, where competition from host germ cells results in offspring derived from host cells and ESCs, necessitating extensive breeding of chimeras and genotyping to identify germline. The germline transmission process is also complicated by variability in the actual number of ESCs that colonize the germline niche and the proportion that are germline competent. To validate the PH approach we used ESC lines derived from 129 F1, BALB/cByJ, and BTBR backgrounds as well as an iPS line. Resulting chimeric males produced 194 offspring, all paternally derived from the introduced stem cells, with no offspring being derived from the host genome. We further tested this approach using eleven genetically modified C57BL/6N ESC lines (International Knockout Mouse Consortium. ESC germline transmission was observed in 9/11 (82% lines using PH blastocysts, compared to 6/11 (55% when conventional host blastocysts were used. Furthermore, less than 35% (83/240 of mice born in the first litters from conventional chimeras were confirmed to be of ESC-origin. By comparison, 100% (137/137 of the first litter offspring of PH chimeras were confirmed as ESC-derived. Together, these data demonstrate that the PH approach increases the probability of germline transmission and speeds the generation of ESC derived animals from chimeras. Collectively, this approach reduces the time and costs inherent in the

  12. Evaluation of Glycemic and Lipid Profile of Offspring of Diabetic Wistar Rats Treated with Malpighia emarginata Juice

    Directory of Open Access Journals (Sweden)

    Sandra M. Barbalho

    2011-01-01

    Full Text Available Knowing that maternal diabetes is related to hyperglycemia and fetal hyperinsulinemia, which affect the lipid metabolism, the aim of this study was to evaluate the effects of Malpighia emarginata (acerola juice on the glycemic and lipid profile of offspring of diabetic and nondiabetic Wistar rats. The adult offspring of non-diabetic dams and of dams with severe streptozotocin-induced diabetes were divided into groups: G1, offspring (of control dams treated with water, G2, offspring (of diabetic dams treated with water, G3, male offspring (of control dams treated with acerola juice, and G4, male offspring (of diabetic dams treated with acerola juice. The offspring of diabetic dams treated with acerola juice showed significantly decreased levels of glucose, cholesterol, triglycerides, and increased HDL-c. The use of acerola juice is a potential strategy to aid in the prevention of DM and dyslipidemia and its complications or to act as an auxiliary in the treatment of these diseases.

  13. Offspring caregivers' depression affected by intergenerational disagreements on preferred living arrangement for the elderly: A phenomena with Chinese characteristic.

    Science.gov (United States)

    Guo, Lihua; Zhang, Jie; Ma, Wei; Sha, Xiaojuan; Yi, Xiangren; Zhang, Bingyin; Wang, Chunping; Wang, Shumei

    2015-01-01

    This study aimed to explore whether the depression of offspring caregivers can be affected by the intergenerational disagreements on preferred living arrangements for the elderly, and the extent of this influence. A total of 875 participants from five urban neighborhoods were investigated in a cross-sectional survey in Jinan, China. Depressive symptoms were assessed by the Self-rating Depression Scale (SDS). Multiple stratification was performed based on participants' characteristics, then generalized linear models (GLM) were used to adjust confounding factor and analyze the effect of the intergenerational disagreements on depressive symptoms among participants with different characteristics. The intergenerational disagreements on preferred living arrangements for the elderly greatly impact on offspring caregivers' depressive symptoms. Especially in the following two situations: (1) in the case of older adults were relatively independent and offspring caregivers had to co-reside with older adults against their own will, the max mean difference on the depression measures was up to 10.603 (pcare older adults against their own will, the max mean difference on the depression measures was up to 8.937 (pelderly have negative effect on offspring caregivers' depressive symptoms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Maternal exposure to the holocaust and health complaints in offspring.

    Science.gov (United States)

    Flory, Janine D; Bierer, Linda M; Yehuda, Rachel

    2011-01-01

    Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and self-reported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring's own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved.

  15. Complex offspring size effects: variations across life stages and between species.

    Science.gov (United States)

    Sun, Zhao; Hamel, Jean-François; Parrish, Christopher C; Mercier, Annie

    2015-03-01

    Classical optimality models of offspring size and number assume a monotonically increasing relationship between offspring size and performance. In aquatic organisms with complex life cycles, the size-performance function is particularly hard to grasp because measures of performance are varied and their relationships with size may not be consistent throughout early ontogeny. Here, we examine size effects in premetamorphic (larval) and postmetamorphic (juvenile) stages of brooding marine animals and show that they vary contextually in strength and direction during ontogeny and among species. Larger offspring of the sea anemone Urticina felina generally outperformed small siblings at the larval stage (i.e., greater settlement and survival rates under suboptimal conditions). However, results differed when analyses were conducted at the intrabrood versus across-brood levels, suggesting that the relationship between larval size and performance is mediated by parentage. At the juvenile stage (15 months), small offspring were less susceptible than large ones to predation by subadult nudibranchs and both sizes performed similarly when facing adult nudibranchs. In a sympatric species with a different life history (Aulactinia stella), all juveniles suffered similar predation rates by subadult nudibranchs, but smaller juveniles performed better (lower mortalities) when facing adult nudibranchs. Size differences in premetamorphic performance of U. felina were linked to total lipid contents of larvae, whereas size-specific predation of juvenile stages followed the general predictions of the optimal foraging strategy. These findings emphasize the challenge in gathering empirical support for a positive monotonic size-performance function in taxa that exhibit complex life cycles, which are dominant in the sea.

  16. Transplantation of adult mouse iPS cell-derived photoreceptor precursors restores retinal structure and function in degenerative mice.

    Directory of Open Access Journals (Sweden)

    Budd A Tucker

    2011-04-01

    Full Text Available This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs, could be used to produce retinal precursors and subsequently photoreceptor cells for retinal transplantation to restore retinal function in degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse ES cells, adult dsRed iPSCs expressed the pluripotency genes SSEA1, Oct4, Sox2, KLF4, c-Myc and Nanog. Following transplantation into the eye of immune-compromised retinal degenerative mice these cells proceeded to form teratomas containing tissue comprising all three germ layers. At 33 days post-differentiation a large proportion of the cells expressed the retinal progenitor cell marker Pax6 and went on to express the photoreceptor markers, CRX, recoverin, and rhodopsin. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for transplantation and treatment of retinal degenerative disease.

  17. Early Life Fructose Exposure and Its Implications for Long-Term Cardiometabolic Health in Offspring.

    Science.gov (United States)

    Zheng, Jia; Feng, Qianyun; Zhang, Qian; Wang, Tong; Xiao, Xinhua

    2016-11-01

    It has become increasingly clear that maternal nutrition can strongly influence the susceptibility of adult offspring to cardiometabolic disease. For decades, it has been thought that excessive intake of fructose, such as sugar-sweetened beverages and foods, has been linked to increased risk of obesity, type 2 diabetes, and cardiovascular disease in various populations. These deleterious effects of excess fructose consumption in adults are well researched, but limited data are available on the long-term effects of high fructose exposure during gestation, lactation, and infancy. This review aims to examine the evidence linking early life fructose exposure during critical periods of development and its implications for long-term cardiometabolic health in offspring.

  18. Age, pathogen exposure, but not maternal care shape offspring immunity in an insect with facultative family life.

    Science.gov (United States)

    Vogelweith, Fanny; Körner, Maximilian; Foitzik, Susanne; Meunier, Joël

    2017-03-07

    To optimize their resistance against pathogen infection, individuals are expected to find the right balance between investing into the immune system and other life history traits. In vertebrates, several factors were shown to critically affect the direction of this balance, such as the developmental stage of an individual, its current risk of infection and/or its access to external help such as parental care. However, the independent and/or interactive effects of these factors on immunity remain poorly studied in insects. Here, we manipulated maternal presence and pathogen exposure in families of the European earwig Forficula auricularia to measure whether and how the survival rate and investment into two key immune parameters changed during offspring development. The pathogen was the entomopathogenic fungus Metarhizium brunneum and the immune parameters were hemocyte concentration and phenol/pro-phenoloxidase enzyme activity (total-PO). Our results surprisingly showed that maternal presence had no effect on offspring immunity, but reduced offspring survival. Pathogen exposure also lowered the survival of offspring during their early development. The concentration of hemocytes and the total-PO activity increased during development, to be eventually higher in adult females compared to adult males. Finally, pathogen exposure overall increased the concentration of hemocytes-but not the total-PO activity-in adults, while it had no effect on these measures in offspring. Our results show that, independent of their infection risk and developmental stage, maternal presence does not shape immune defense in young earwigs. This reveals that pathogen pressure is not a universal evolutionary driver of the emergence and maintenance of post-hatching maternal care in insects.

  19. Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance.

    Science.gov (United States)

    Nygaard, Unni Cecilie; Vinje, Nina Eriksen; Samuelsen, Mari; Andreassen, Monica; Groeng, Else-Carin; Bølling, Anette Kocbach; Becher, Rune; Lovik, Martinus; Bodin, Johanna

    2015-09-01

    The impact of early life exposure to bisphenol A (BPA) through drinking water was investigated in mouse models of respiratory allergy, food allergy and oral tolerance. Balb/c mice were exposed to BPA (0, 10 or 100 μg/ml), and the offspring were intranasally exposed to the allergen ovalbumin (OVA). C3H/HeJ offspring were sensitized with the food allergen lupin by intragastric gavage, after exposure to BPA (0, 1, 10 or 100 μg/ml). In separate offspring, oral tolerance was induced by gavage of 5 mg lupin one week before entering the protocol for the food allergy induction. In the airway allergy model, BPA (100 μg/ml) caused increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and a trend of increased OVA-specific IgE levels. In the food allergy and tolerance models, BPA did not alter the clinical anaphylaxis or antibody responses, but induced alterations in splenocyte cytokines and decreased mouse mast cell protease (MMCP)-1 serum levels. In conclusion, early life exposure to BPA through drinking water modestly augmented allergic responses in a mouse model of airway allergy only at high doses, and not in mouse models for food allergy and tolerance. Thus, our data do not support that BPA promotes allergy development at exposure levels relevant for humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

    Science.gov (United States)

    Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

    2012-12-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Inbreeding depression in an insect with maternal care: influences of family interactions, life stage and offspring sex.

    Science.gov (United States)

    Meunier, J; Kölliker, M

    2013-10-01

    Although inbreeding is commonly known to depress individual fitness, the severity of inbreeding depression varies considerably across species. Among the factors contributing to this variation, family interactions, life stage and sex of offspring have been proposed, but their joint influence on inbreeding depression remains poorly understood. Here, we demonstrate that these three factors jointly shape inbreeding depression in the European earwig, Forficula auricularia. Using a series of cross-breeding, split-clutch and brood size manipulation experiments conducted over two generations, we first showed that sib mating (leading to inbred offspring) did not influence the reproductive success of earwig parents. Second, the presence of tending mothers and the strength of sibling competition (i.e. brood size) did not influence the expression of inbreeding depression in the inbred offspring. By contrast, our results revealed that inbreeding dramatically depressed the reproductive success of inbred adult male offspring, but only had little effect on the reproductive success of inbred adult female offspring. Overall, this study demonstrates limited effects of family interactions on inbreeding depression in this species and emphasizes the importance of disentangling effects of sib mating early and late during development to better understand the evolution of mating systems and population dynamics. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  2. The role of depression in the differential effect of childhood parental divorce on male and female adult offspring suicide attempt risk.

    Science.gov (United States)

    Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

    2010-09-01

    In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized.

  3. Association between maternal age at childbirth and child and adult outcomes in the offspring: a prospective study in five low-income and middle-income countries (COHORTS collaboration).

    Science.gov (United States)

    Fall, Caroline H D; Sachdev, Harshpal Singh; Osmond, Clive; Restrepo-Mendez, Maria Clara; Victora, Cesar; Martorell, Reynaldo; Stein, Aryeh D; Sinha, Shikha; Tandon, Nikhil; Adair, Linda; Bas, Isabelita; Norris, Shane; Richter, Linda M

    2015-07-01

    Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low-income and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. We aimed to examine both child and adult outcomes in five LMICs. In this prospective study, we pooled data from COHORTS (Consortium for Health Orientated Research in Transitioning Societies)-a collaboration of five birth cohorts from LMICs (Brazil, Guatemala, India, the Philippines, and South Africa), in which mothers were recruited before or during pregnancy, and the children followed up to adulthood. We examined associations between maternal age and offspring birthweight, gestational age at birth, height-for-age and weight-for-height Z scores in childhood, attained schooling, and adult height, body composition (body-mass index, waist circumference, fat, and lean mass), and cardiometabolic risk factors (blood pressure and fasting plasma glucose concentration), along with binary variables derived from these. Analyses were unadjusted and adjusted for maternal socioeconomic status, height and parity, and breastfeeding duration. We obtained data for 22 188 mothers from the five cohorts, enrolment into which took place at various times between 1969 and 1989. Data for maternal age and at least one outcome were available for 19 403 offspring (87%). In unadjusted analyses, younger (≤19 years) and older (≥35 years) maternal age were associated with lower birthweight, gestational age, child nutritional status, and schooling. After adjustment, associations with younger maternal age remained for low birthweight (odds ratio [OR] 1·18 (95% CI 1·02-1·36)], preterm birth (1·26 [1·03-1·53]), 2-year stunting (1·46 [1·25-1·70]), and failure to complete secondary schooling (1·38 [1·18-1·62]) compared with mothers aged 20-24 years. After adjustment, older maternal age remained associated with increased risk of preterm birth (OR 1

  4. Intrauterine Exposure to Maternal Stress Alters Bdnf IV DNA Methylation and Telomere Length in the Brain of Adult Rat Offspring

    Science.gov (United States)

    Blaze, Jennifer; Asok, Arun; Borrelli, Kristyn; Tulbert, Christine; Bollinger, Justin; Ronca Finco, April E.; Roth, Tania L.

    2017-01-01

    DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could contribute to the long-term effects of intrauterine exposure to maternal stress on offspring behavioral outcomes. Here, we measured methylation of Brain-derived neurotrophic factor (Bdnf), a gene important in development and plasticity, and telomere length in the brains of adult rat male and female offspring whose mothers were exposed to unpredictable and variable stressors throughout gestation. Males exposed to prenatal stress had greater methylation (Bdnf IV) in the medial prefrontal cortex (mPFC) compared to non-stressed controls. Further, prenatally-stressed males had shorter telomeres than controls in the mPFC. This study provides the first evidence in a rodent model of an association between prenatal stress exposure and subsequent shorter brain telomere length. Together findings indicate a long-term impact of prenatal stress on DNA methylation and telomere biology with relevance for behavioral and health outcomes, and contribute to a growing literature linking stress to intergenerational epigenetic alterations and changes in telomere length.

  5. Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

    Directory of Open Access Journals (Sweden)

    Clint Gray

    Full Text Available Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L. Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L, with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]. Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger, member 3 (SLC9A3 together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young.

  6. Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

    Science.gov (United States)

    Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

    2013-01-01

    Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

  7. In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei, E-mail: weiwang2@illinois.edu; Hafner, Katlyn S., E-mail: katlynhafner@gmail.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2014-04-15

    Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in

  8. In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

    International Nuclear Information System (INIS)

    Wang, Wei; Hafner, Katlyn S.; Flaws, Jodi A.

    2014-01-01

    Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in

  9. Pathways to suicide-related behavior in offspring of mothers with depression: the role of offspring psychopathology.

    Science.gov (United States)

    Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

    2015-05-01

    Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers' first 11 years of their child's life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology

    Science.gov (United States)

    Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M.; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

    2015-01-01

    Objective Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Method Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Conclusion Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. PMID:25901775

  11. Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

    Directory of Open Access Journals (Sweden)

    Béringue Vincent

    2010-07-01

    Full Text Available Abstract Background The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.

  12. Is the association between offspring intelligence and parents' educational attainment influenced by schizophrenia or mood disorder in parents?

    DEFF Research Database (Denmark)

    Greve, Aja Neergaard; Mors, Ole; Mortensen, Erik Lykke

    2017-01-01

    for developing schizophrenia. Based on these findings, we aim to investigate if the association between educational achievement in parents and intelligence in their offspring is influenced by schizophrenia or mood disorder in parents. In a large population-based sample of young adult male conscripts (n = 156......,531) the presence of a mental disorder in the parents were associated with significantly lower offspring scores on a test of general intelligence, the Børge Priens Prøve (BPP), and higher educational attainment in parents was significantly associated with higher BPP test scores in offspring. A significant...... interaction suggested that the positive association between maternal education and offspring intelligence was stronger in offspring of mothers with schizophrenia compared to the control group (p = 0.03). The associations between parental education and offspring intelligence are also observed when restricting...

  13. Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats.

    Science.gov (United States)

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Piryaei, Abbas; Ghasemi, Asghar

    2018-05-01

    What is the central question of this study? Does fetal hypothyroidism in rats alter uterine contractions and structure in the adult offspring? What is the main finding and its importance? Our study indicated that maternal hypothyroidism during pregnancy increased gestational length and decreased litter size. In addition, maternal hypothyroidism caused delayed puberty onset, irregular uterine contractions and histological changes in the uterus in the female offspring. This model might contribute to a better understanding of the cellular and molecular mechanisms involved in uterine contractions in fetal hypothyroidism, studies which are not possible in humans, and might help to establish therapeutic methods for these disorders observed in uterine contractions. Thyroid hormones play an essential role in fetal growth. Hypothyroidism impairs reproductive function in both humans and animals. The aim of this study was to assess the effects of fetal hypothyroidism on uterine smooth muscle contraction and structure in the adult offspring. The control group of female Wistar rats consumed tap water, whereas the hypothyroid group received water containing 0.025% of 6-propyl-2-thiouracial throughout gestation from mating until delivery. Isometric contractility and histological changes in uterine tissue were evaluated in the adult female offspring. We tested the effects of carbachol (10 -10 -10 -3  m) and oxytocin (10 -13 -10 -8  m) on uterine smooth muscle contraction in the fetal hypothyroid (FH) and control groups. Compared with control uteri, carbachol induced contractions with lower amplitude in the FH group (area under the curve: 1820.0 ± 250.0 versus 1370.0 ± 125.0 a.u., control versus FH group, respectively, P muscle layer and the cross-sectional area of the uterus were also significantly lower in the FH group. Gestational length was longer and litter size smaller in FH rats compared with control animals; FH offspring also had delayed puberty. In conclusion

  14. Effects of perinatal exposure to low doses of tributyltin chloride on pregnancy outcome and postnatal development in mouse offspring.

    Science.gov (United States)

    Si, Jiliang; Li, Jie; Zhang, Fengmei; Li, Guozhen; Xin, Quanbin; Dai, Bingqin

    2012-10-01

    Tributyltin (TBT), an endocrine-disrupting chemical, is well known to induce imposex in female gastropods. In this study, we assessed the effects of low doses of tributyltin chloride (TBTCl) on dams and their offspring. Pregnant mice were administered by gavage with 0, 1, 10, or 100 μg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. There were no TBT treatment-related deaths or clinical signs of toxicity for dams, and no treatment-related effects on body weight, litter sizes, gestational length of dams, and sex ratio, lactational body weight, postnatal survival, age at eruption of incisors, and eye opening of pups. However, at 100 μg/kg, TBTCl retarded the testes descent of male offspring. Behavioral tests showed a significant delay in cliff-drop aversion response in offspring of 10 and 100 μg/kg groups, but no significant difference in the righting reflex between control and TBT-exposed offspring was detectable. These results indicate that neurobehavioral toxicity seems to be one sensitive indicator to assess the risk of low doses of TBT. Copyright © 2011 Wiley Periodicals, Inc.

  15. Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study.

    Science.gov (United States)

    Sanchez-Gistau, Vanessa; Romero, Soledad; Moreno, Dolores; de la Serna, Elena; Baeza, Inmaculada; Sugranyes, Gisela; Moreno, Carmen; Sanchez-Gutierrez, Teresa; Rodriguez-Toscano, Elisa; Castro-Fornieles, Josefina

    2015-10-01

    Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. SZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The effects of unrelated offspring whistle calls on capybaras (Hydrochoerus hydrochaeris

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    E Dos Santos

    Full Text Available Parent-offspring vocal communication, such as the isolation call, is one of the essential adaptations in mammals that adjust parental responsiveness. Thus, our aim was to test the hypothesis that the function of the capybara infants' whistle is to attract conspecifics. We designed a playback experiment to investigate the reaction of 20 adult capybaras (seven males and 13 females to pups' whistle calls – recorded from unrelated offspring – or to bird song, as control. The adult capybaras promptly responded to playback of unrelated pup whistles, while ignoring the bird vocalisation. The adult capybaras took, on average, 2.6 ± 2.5 seconds (s to show a response to the whistles, with no differences between males and females. However, females look longer (17.0 ± 12.9 s than males (3.0 ± 7.2 s toward the sound source when playing the pups' whistle playback. The females also tended to approach the playback source, while males showed just a momentary interruption of ongoing behaviour (feeding. Our results suggest that capybara pups' whistles function as the isolation call in this species, but gender influences the intensity of the response.

  17. Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.

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    Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi

    2015-01-01

    Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The generation of live offspring from vitrified oocytes.

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    L Gabriel Sanchez-Partida

    Full Text Available Oocyte cryopreservation is extremely beneficial for assisted reproductive technologies, the treatment of infertility and biotechnology and offers a viable alternative to embryo freezing and ovarian grafting approaches for the generation of embryonic stem cells and live offspring. It also offers the potential to store oocytes to rescue endangered species by somatic cell nuclear transfer and for the generation of embryonic stem cells to study development in these species. We vitrified mouse oocytes using a range of concentrations of trehalose (0 to 0.3 M and demonstrated that 0.1 and 0.3 M trehalose had similar developmental rates, which were significantly different to the 0.2 M cohort (P<0.05. As mitochondria are important for fertilisation outcome, we observed that the clustering and distribution of mitochondria of the 0.2 M cohort were more affected by vitifrication than the other groups. Nevertheless, all 3 cohorts were able to develop to blastocyst, following in vitro fertilisation, although developmental rates were better for the 0.1 and 0.3 M cohorts than the 0.2 M cohort (P<0.05. Whilst blastocysts gave rise to embryonic stem-like cells, it was apparent from immunocytochemistry and RT-PCR that these cells did not demonstrate true pluripotency and exhibited abnormal karyotypes. However, they gave rise to teratomas following injection into SCID mice and differentiated into cells of each of the germinal layers following in vitro differentiation. The transfer of 2-cell embryos from the 0.1 and 0.3 M cohorts resulted in the birth of live offspring that had normal karyotypes (9/10. When 2-cell embryos from vitrified oocytes underwent vitrification, and were thawed and transferred, live offspring were obtained that exhibited normal karyotypes, with the exception of one offspring who was larger and died at 7 months. We conclude that these studies highlight the importance of the endometrial environment for the maintenance of genetic stability and

  19. Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring.

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    Ferreira, Diorginis Soares; Liu, Yuri; Fernandes, Mariana Pinheiro; Lagranha, Claudia Jacques

    2016-10-01

    Studies in humans and animal models have established a close relationship between early environment insult and subsequent risk of development of non-communicable diseases, including the cardiovascular. Whereas experimental evidences highlight the early undernutrition and the late cardiovascular disease relation, the central mechanisms linking the two remain unknown. Owing to the oxidative balance influence in several pathologies, the aim of the present study was to evaluate the effects of maternal undernutrition (i.e. a low-protein (LP) diet) on oxidative balance in the brainstem. Male rats from mothers fed with an LP diet (8% casein) throughout the perinatal period (i.e. gestation and lactation) showed 10× higher lipid peroxidation levels than animals treated with normoprotein (17% casein) at 100 days of age. In addition, we observed the following reductions in enzymatic activities: superoxide dismutase, 16%; catalase, 30%; glutathione peroxidase, 34%; glutathione-S-transferase, 51%; glutathione reductase, 23%; glucose-6-phosphate dehydrogenase, 31%; and in non-enzymatic glutathione system, 46%. This study is the first to focus on the role of maternal LP nutrition in oxidative balance in a central nervous system structure responsible for cardiovascular control in adult rats. Our data observed changes in oxidative balance in the offspring, therefore, bring a new concept related to early undernutrition and can help in the development of a new clinical strategy to combat the effects of nutritional insult. Wherein the central oxidative imbalance is a feasible mechanism underlying the hypertension risk in adulthood triggered by maternal LP diet.

  20. Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring.

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    Baydas, Giyasettin; Koz, Sema T; Tuzcu, Mehmet; Nedzvetsky, Victor S; Etem, Ebru

    2007-05-01

    In this study, we suggest that chronic maternal hyperhomocysteinemia results in learning deficits in the offspring due to delayed brain maturation and altered expression pattern of neural cell adhesion molecule. Although the deleterious effects of hyperhomocysteinemia were extensively investigated in the adults, there is no clear evidence suggesting its action on the developing fetal rat brain and cognitive functions of the offspring. Therefore, in the present work we aimed to investigate effects of maternal hyperhomocysteinemia on the fetal brain development and on the behavior of the offspring. A group of pregnant rats received daily methionine (1 g/kg body weight) dissolved in drinking water to induce maternal hyperhomocysteinemia, starting in the beginning of gestational day 0. The levels of glial fibrillary acidic protein, S100B protein, and neural cell adhesion molecule were determined in the tissue samples from the pups. Learning and memory performances of the young-adult offsprings were tested using Morris water maze test. There were significant reductions in the expressions of glial fibrillary acidic protein and S100B protein in the brains of maternally hyperhomocysteinemic pups on postnatal day 1, suggesting that hyperhomocysteinemia delays brain maturation. In conclusion, maternal hyperhomocysteinemia changes the expression pattern of neural cell adhesion molecule and therefore leads to an impairment in the learning performance of the offspring.

  1. A new and fast technique to generate offspring after germ cells transplantation in adult fish: the Nile tilapia (Oreochromis niloticus model.

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    Samyra M S N Lacerda

    Full Text Available BACKGROUND: Germ cell transplantation results in fertile recipients and is the only available approach to functionally investigate the spermatogonial stem cell biology in mammals and probably in other vertebrates. In the current study, we describe a novel non-surgical methodology for efficient spermatogonial transplantation into the testes of adult tilapia (O. niloticus, in which endogenous spermatogenesis had been depleted with the cytostatic drug busulfan. METHODOLOGY/PRINCIPAL FINDINGS: Using two different tilapia strains, the production of fertile spermatozoa with donor characteristics was demonstrated in adult recipient, which also sired progeny with the donor genotype. Also, after cryopreservation tilapia spermatogonial cells were able to differentiate to spermatozoa in the testes of recipient fishes. These findings indicate that injecting germ cells directly into adult testis facilitates and enable fast generation of donor spermatogenesis and offspring compared to previously described methods. CONCLUSION: Therefore, a new suitable methodology for biotechnological investigations in aquaculture was established, with a high potential to improve the production of commercially valuable fish, generate transgenic animals and preserve endangered fish species.

  2. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

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    Laig-Webster, M.; Lim, M.E.; Chehab, F.F. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  3. Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model.

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    Heidi Marjonen

    Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in

  4. Antagonistic parent-offspring co-adaptation.

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    Mathias Kölliker

    2010-01-01

    Full Text Available In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  5. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

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    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique; Khorsi-Cauet, Hafida; Abdennebi-Najar, Latifa

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring's birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

  6. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

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    Julie Reygner

    Full Text Available Increasing evidence indicates that chlorpyrifos (CPF, an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1 or 3.5 mg/kg/day (CPF3.5 with free access to inulin (10g/L in drinking water. Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs in the colon, were analyzed at postnatal day 60 in the offspring (PND 60. CPF3.5 increased offspring's birth body weight (BW but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

  7. [Isolation, purification and primary culture of adult mouse cardiac fibroblasts].

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    Li, Rujun; Gong, Kaizheng; Zhang, Zhengang

    2017-01-01

    Objective To establish a method for primary culture of adult mouse cardiac fibroblasts. Methods Myocardial tissues from adult mice were digested with 1 g/L trypsin and 0.8 g/L collagenase IV by oscillating water bath for a short time repeatedly. Cardiac fibroblasts and myocardial cells were isolated with differential adhesion method. Immunofluorescence staining was used to assess the purity of cardiac fibroblasts. The cell morphology was observed under an inverted phase contrast microscope. The proliferation of cardiac fibroblasts was analyzed by growth curve and CCK-8 assay. The Smad2/3 phosphorylation induced by TGF-β1 was detected by Western blotting. Results After 90 minutes of differential adhesion, adherent fibroblasts formed spherical cell mass and after 3 days, cells were spindle-shaped and proliferated rapidly. Cells were confluent after 5 days and the growth curve presented nearly "S" shape. The positive expression rate of vimentin was 95%. CCK-8 assay showed that the optimal cell proliferating activity was found from day 3 to day 5. The level of phosphorylated Smad2/3 obviously increased at the second passage induced by TGF-β1. Conclusion This method is economical and stable to isolate cardiac fibroblasts with high activity and high purity from adult mice.

  8. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

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    Salomäki, Henriikka; Heinäniemi, Merja; Vähätalo, Laura H; Ailanen, Liisa; Eerola, Kim; Ruohonen, Suvi T; Pesonen, Ullamari; Koulu, Markku

    2014-01-01

    Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. Female mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue. This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  9. Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

    Science.gov (United States)

    2014-01-01

    Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

  10. Long-Term Consequences for Offspring of Paternal Diabetes and Metabolic Syndrome

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    Benigno Linares Segovia

    2012-01-01

    Full Text Available Background. Recent studies have reported an increase in the prevalence of obesity and metabolic syndrome in children and adolescents. However, few have focused how diabetes mellitus and metabolic syndrome together in parents can influence on obesity and metabolic disturbances in offspring. Objective. To know the risk obesity and metabolic disturbance in children, adolescents, and young adults whose parents have diabetes mellitus and metabolic syndrome. Methods. A comparative survey was made in healthy children of parents with diabetes mellitus and metabolic syndrome compared with offspring of healthy parents. We performed anthropometry and evaluated blood pressure, glucose, total cholesterol, HDL cholesterol, and triglycerides levels in plasma. We registered parent antecedents to diabetes mellitus and metabolic syndrome and investigated the prevalence of overweight, obesity, and metabolic disturbances in offspring. Results. We studied 259 subjects of 7 to 20 years of age. The prevalence of overweight and obesity was 27% and 37%, respectively. The highest proportion of BMI >95th of the entire group was found in offspring with both diabetic parents. Glucose and total cholesterol levels were lower in the group with healthy parents compared with the group with diabetic mother and metabolic syndrome but with healthy father. HDL cholesterol was higher in the group with both healthy parents than in the group with diabetic mother and metabolic syndrome but healthy father. Conclusions. The offspring of parents with diabetes plus metabolic syndrome showed higher proportion of variables related to metabolic syndrome compared with healthy parents.

  11. Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

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    Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

    2011-01-01

    Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

  12. [Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation].

    Science.gov (United States)

    Bezlepkin, V G; Vasil'eva, G V; Lomaeva, M G; Sirota, N P; Gaziev, A I

    2000-01-01

    By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.

  13. Resource Elasticity of Offspring Survival and the Optimal Evolution of Sex Ratios

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    Wang, Rui-Wu; Wang, Ya-Qiang; He, Jun-Zhou; Li, Yao-Tang

    2013-01-01

    The fitness of any organisms includes the survival and reproductive rate of adults and the survival of their offspring. Environmental selection pressures might not affect these two aspects of an organism equally. Assuming that an organism first allocates its limited resources to maintain its survival under environmental selection pressure, our model, based on the evolutionarily stable strategy theory, surprisingly shows that the sex ratio is greatly affected by the environmental pressure intensity and by the reproductive resource elasticity of offspring survival. Moreover, the concept of the resource elasticity of offspring survival intrinsically integrates the ecological concepts of K selection and r selection. The model shows that in a species with reproductive strategy K, increased environmental selection pressure will reduce resource allocation to the male function. By contrast, in a species with reproductive strategy r, harsher environmental selection pressure will increase allocation to the male function. The elasticity of offspring survival might vary not only across species, but also across many other factors affecting the same species (e.g., age structure, spatial heterogeneity), which explains sex ratio differences across species or age structures and spatial heterogeneity in the same species. PMID:23468826

  14. Perinatal exposure to environmental tobacco smoke is associated with changes in DNA methylation that precede the adult onset of lung disease in a mouse model.

    Science.gov (United States)

    Cole, Elizabeth; Brown, Traci A; Pinkerton, Kent E; Postma, Britten; Malany, Keegan; Yang, Mihi; Kim, Yang Jee; Hamilton, Raymond F; Holian, Andrij; Cho, Yoon Hee

    2017-08-01

    Prenatal and early-life environmental tobacco smoke (ETS) exposure can induce epigenetic alterations associated with inflammation and respiratory disease. The objective of this study was to address the long-term epigenetic consequences of perinatal ETS exposure on latent respiratory disease risk, which are still largely unknown. C57BL/6 mice were exposed to prenatal and early-life ETS; offspring lung pathology, global DNA, and gene-specific methylation were measured at two adult ages. Significant alterations in global DNA methylation and promoter methylation of IFN-γ and Thy-1 were found in ETS-exposed offspring at 10-12 and 20 weeks of age. These sustained epigenetic alterations preceded the onset of significant pulmonary pathologies observed at 20 weeks of age. This study suggests that perinatal ETS exposure induces persistent epigenetic alterations in global DNA, as well as IFN-γ and Thy-1 promoter methylation that precede the adult onset of fibrotic lung pathology. These epigenetic findings could represent potential biomarkers of latent respiratory disease risk.

  15. Evidence of Oxidative Shielding of Offspring in a Wild Mammal

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    Emma I. K. Vitikainen

    2016-05-01

    Full Text Available Oxidative damage has been proposed as a potential mechanism underlying a life history tradeoff between survival and reproduction. However, evidence that reproduction is associated with increased oxidative damage is equivocal, and some studies have found that breeding females exhibit reduced, rather than elevated, levels of oxidative damage compared to equivalent non-breeders. Recently it was hypothesized that oxidative damage could have negative impacts on developing offspring, and that mothers might down-regulate oxidative damage during reproduction to shield their offspring from such damage. We tested this hypothesis through a longitudinal study of adult survival, reproduction, and oxidative damage in wild banded mongooses (Mungos mungo in Uganda. High levels of oxidative damage as measured by malondialdehyde (MDA were associated with reduced survival in both sexes. Levels of protein carbonyls were not linked to survival. Mothers showed reduced levels of MDA during pregnancy, and individuals with higher MDA levels gestated fewer offspring and had lower pup survival. These results suggest that maternal oxidative damage has transgenerational costs, and are consistent with the idea that mothers may attempt to shield their offspring from particularly harmful types of oxidative damage during pregnancy. We suggest that further advance in understanding of life history variation could benefit from theoretical and empirical exploration of the potential transgenerational costs of reproduction.

  16. Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

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    Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

    2012-12-01

    Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

  17. Parent-offspring correlations in pedometer-assessed physical activity.

    Directory of Open Access Journals (Sweden)

    David Jacobi

    Full Text Available Physical activity is a major component of a healthy lifestyle in youth and adults. To identify determinants of this complex behavior is an important research objective in the process of designing interventions to promote physical activity at population level. In addition to individual determinants, there is evidence documenting familial influences on physical activity. However, the few studies that have addressed this issue with objective measures did not provide data on parent-offspring physical activity relationships throughout childhood and adolescence. The purpose of this study was to assess familial correlations in pedometer-assessed physical activity.We measured ambulatory activity in 286 French nuclear families (283 mothers, 237 fathers, and 631 children aged 8-18 years by pedometer recordings (Yamax Digiwalker DW 450 over a week. Correlations were computed with their 95% confidence intervals (CI for spouse pairs, siblings, mother-offspring, and father-offspring. Data were expressed as steps per day and computed both for the full recording period and separately for weekdays and weekends.The correlations were the highest between siblings (r=0.28, 95%CI: 0.17-0.38. Parent-offspring correlations were significant in mothers (r=0.21, 95%CI: 0.12-0.30, especially between mothers and daughters (r=0.24, 95%CI: 0.12-0.36 vs. r=0.18, 95%CI: 0.05-0.31 for sons, but were almost nonexistent in fathers. Correlations were generally higher on weekend days compared to weekdays. Mother-offspring correlations did not decrease with increasing age of children (r=0.17, 95%CI: 0.00-0.34 in 8-11-year-olds, r=0.20, 95%CI: 0.07-0.33 in 12-15-year-olds, and r=0.25, 95%CI: 0.07-0.39 in ≥16-year-olds. Finally, between-spouse correlations were significant only during weekend days (r=0.14, 95%CI: 0.01-0.27.Ambulatory activity correlated within families, with a possible mother effect. Mother-offspring correlations remained significant through the transition from

  18. Genetic and environmental influences on the familial transmission of externalizing disorders in adoptive and twin offspring.

    Science.gov (United States)

    Hicks, Brian M; Foster, Katherine T; Iacono, William G; McGue, Matt

    2013-10-01

    Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects. To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission. Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences. Participants were recruited from the community and assessed at a university laboratory. A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years). Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. RESULTS There was a medium effect for the transmission of the general externalizing liability for biological parents (r = 0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (r = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a2 = 0.61) but also exhibited significant shared environmental influences (c2 = 0.20). Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability

  19. The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

    Science.gov (United States)

    Glastras, Sarah J.; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T.; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A.; Saad, Sonia

    2017-01-01

    Aims/Hypothesis Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Methods Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. Results HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Conclusion Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity. PMID:28225809

  20. The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.

    Directory of Open Access Journals (Sweden)

    Sarah J Glastras

    Full Text Available Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease.Female C57BL/6 mice were fed high-fat diet (HFD for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p. or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32.HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity.Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

  1. Parents' perceptions on offspring risk and prevention of anxiety and depression: a qualitative study.

    Science.gov (United States)

    Festen, Helma; Schipper, Karen; de Vries, Sybolt O; Reichart, Catrien G; Abma, Tineke A; Nauta, Maaike H

    2014-01-01

    Offspring of patients with anxiety or depression are at high risk for developing anxiety or depression. Despite the positive findings regarding effectiveness of prevention programs, recruitment for prevention activities and trials is notoriously difficult. Our randomized controlled prevention trial was terminated due to lack of patient inclusion. Research on mentally-ill parents' perceptions of offspring's risk and need for preventive intervention may shed light on this issue, and may enhance family participation in prevention activities and trials. Qualitative data were collected through semi-structured interviews with 24 parents (patients with anxiety or depression, or their partners). An inductive content analysis of the data was performed. Five research questions were investigated regarding parents' perceptions of anxiety, depression, and offspring risk; anxiety, depression, and parenting; the need for offspring intervention and prevention; and barriers to and experiences with participation in preventive research. Parental perceptions of the impact of parental anxiety and depression on offspring greatly differed. Parents articulated concerns about children's symptomatology, however, most parents did not perceive a direct link between parent symptoms and offspring quality of life. They experienced an influence of parental symptoms on family quality of life, but chose not to discuss that with their children in order to protect them. Parents were not well aware of the possibilities regarding professional help for offspring and preferred parent-focused rather than offspring-focused interventions such as parent psycho-education. Important barriers to participation in preventive research included parental overburden, shame and stigma, and perceived lack of necessity for intervention. This study highlights the importance of educating parents in adult health care. Providing psycho-education regarding offspring risk, communication in the family, and parenting in order

  2. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

    Directory of Open Access Journals (Sweden)

    Henriikka Salomäki

    Full Text Available AIMS: Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. MATERIALS AND METHODS: Female mice were on a high fat diet (HFD prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD and subjected to HFD at adulthood (10-11 weeks. Body weight and several metabolic parameters (e.g. body composition and glucose tolerance were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. RESULTS: Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC was prominently affected both in the neonatal liver and adipose tissue. CONCLUSION: This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  3. Chronic maternal low-protein diet in mice affects anxiety, night-time energy expenditure and sleep patterns, but not circadian rhythm in male offspring

    Science.gov (United States)

    Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decre...

  4. A novel type of self-beating cardiomyocytes in adult mouse ventricles

    International Nuclear Information System (INIS)

    Omatsu-Kanbe, Mariko; Matsuura, Hiroshi

    2009-01-01

    This study was designed to investigate the presence of resident heart cells that are distinct from terminally-differentiated cardiomyocytes. Adult mouse heart was coronary perfused with collagenase, and ventricles were excised and further digested. After spinning cardiomyocyte-containing fractions down, the supernatant fraction was collected and cultured without adding any chemicals. Two to five days after plating, some of rounded cells adhered to the culture dish, gradually changed their shape and then started self-beating. These self-beating cells did not appreciably proliferate but underwent a further morphological maturation process to form highly branched shapes with many projections. These cells were mostly multinucleated, well sarcomeric-organized and expressed cardiac marker proteins, defined as atypically-shaped cardiomyocytes (ACMs). Patch-clamp experiments revealed that ACMs exhibited spontaneous action potentials arising from the preceding slow diastolic depolarization. We thus found a novel type of resident heart cells in adult cardiac ventricles that spontaneously develop into self-beating cardiomyocytes.

  5. Comparing indicators of health and development of singleton young adults conceived with and without assisted reproductive technology.

    Science.gov (United States)

    Halliday, Jane; Wilson, Cate; Hammarberg, Karin; Doyle, Lex W; Bruinsma, Fiona; McLachlan, Robert; McBain, John; Berg, Turi; Fisher, Jane R; Amor, David

    2014-04-01

    To compare outcomes for young adults conceived by assisted reproductive technology (ART) with non-ART-conceived young adults. Cohort study. Not applicable. Mothers and their offspring (aged 18-28 years) conceived by ART; mothers and their non-ART-conceived offspring, randomly selected from the same source population. Structured telephone interviews, one with mothers and another with their young adult offspring. Maternal report on young adult offspring hospitalizations and chronic illness accumulated over the first 18 years of their lives; young adult self-report on perceived current quality of life, body mass index, pubertal development, and educational achievement. Of 1,480 eligible ART mothers, 80% were traced and contacted. Of those, 656 (55%) participated, reporting on 705 ART-conceived offspring; 269 (23%) declined participation and 262 (22%) did not respond. Of the participants, 84% consented to contact with their young adult offspring, of whom 547 (92%) participated. Random-digit dialing recruited 868 non-ART mothers and 549 offspring. Compared with non-ART young adults, the ART group had significant increases in three maternally reported outcomes: 1) hospital admissions, including those in the secondary school years; 2) atopic respiratory conditions; and 3) combined endocrine, nutritional, and metabolic disease ICD-10 category. Young adult reported outcomes were similar for both groups. This study addresses gaps in knowledge of outcomes beyond adolescence for those conceived by ART. Results show few adverse outcomes in this large cohort of young adults, but additional assessment through clinical review is required to address issues unable to be examined in this study. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Perinatal maternal administration of Lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy.

    Directory of Open Access Journals (Sweden)

    Irma Schabussova

    Full Text Available BACKGROUND: The hygiene hypothesis implies that microbial agents including probiotic bacteria may modulate foetal/neonatal immune programming and hence offer effective strategies for primary allergy prevention; however their mechanisms of action are poorly understood. We investigated whether oral administration of Lactobacillus paracasei NCC 2461 to mothers during gestation/lactation can protect against airway inflammation in offspring in a mouse model of birch pollen allergy, and examined the immune mechanisms involved. METHODS: BALB/c mice were treated daily with L. paracasei in drinking water or drinking water alone in the last week of gestation and during lactation. Their offspring were sensitized with recombinant Bet v 1, followed by aerosol challenge with birch pollen extract. RESULTS: Maternal exposure to L. paracasei prevented the development of airway inflammation in offspring, as demonstrated by attenuation of eosinophil influx in the lungs; reduction of IL-5 levels in bronchoalveolar lavage, and in lung and mediastinal lymph node cell cultures; and reduced peribronchial inflammatory infiltrate and mucus hypersecretion. While allergen-specific IgE and IgG antibody levels remained unchanged by the treatment, IL-4 and IL-5 production in spleen cell cultures were significantly reduced upon allergen stimulation in offspring of L. paracasei treated mice. Offspring of L. paracasei supplemented mothers had significantly reduced Bet v 1-specific as well as Concanavalin A-induced responses in spleen and mesenteric lymph node cell cultures, suggesting the modulation of both antigen-specific and mitogen-induced immune responses in offspring. These effects were associated with increased Foxp3 mRNA expression in the lungs and increased TGF-beta in serum. CONCLUSION: Our data show that in a mouse model of birch pollen allergy, perinatal administration of L. paracasei NCC 2461 to pregnant/lactating mothers protects against the development of airway

  7. Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

    Directory of Open Access Journals (Sweden)

    Joyce R.S. Raimundo

    Full Text Available OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi, renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure, cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

  8. Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

    Science.gov (United States)

    Oliveira, V; Silva Junior, S D; de Carvalho, M H C; Akamine, E H; Michelini, L C; Franco, M C

    2017-04-01

    It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

  9. Psychopathology in adolescent offspring of parents with panic disorder, major depression, or both: a 10-year follow-up.

    Science.gov (United States)

    Hirshfeld-Becker, Dina R; Micco, Jamie A; Henin, Aude; Petty, Carter; Faraone, Stephen V; Mazursky, Heather; Bruett, Lindsey; Rosenbaum, Jerrold F; Biederman, Joseph

    2012-11-01

    The authors examined the specificity and course of psychiatric disorders from early childhood through adolescence in offspring of parents with confirmed panic disorder and major depressive disorder. The authors examined rates of psychiatric disorders at 10-year-follow-up (mean age, 14 years) in four groups: offspring of referred parents with panic and depression (N=137), offspring of referred parents with panic without depression (N=26), offspring of referred parents with depression without panic (N=48), and offspring of nonreferred parents with neither disorder (N=80). Follow-up assessments relied on structured interviews with the adolescents and their mothers; diagnoses were rated present if endorsed by either. Parental panic disorder, independently of parental depression, predicted lifetime rates in offspring of multiple anxiety disorders, panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Parental depression independently predicted offspring bipolar, drug use, and disruptive behavior disorders. Parental panic and depression interacted to predict specific phobia and major depressive disorder. Phobias were elevated in all at-risk groups, and depression was elevated in both offspring groups of parents with depression (with or without panic disorder), with the highest rates in the offspring of parents with depression only. Parental depression independently predicted new onset of depression, parental panic disorder independently predicted new onset of social phobia, and the two interacted to predict new onset of specific phobia and generalized anxiety disorder. At-risk offspring continue to develop new disorders as they progress through adolescence. These results support the need to screen and monitor the offspring of adults presenting for treatment of panic disorder or major depressive disorder.

  10. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

    Science.gov (United States)

    Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A; Dalmeijer, Gerdien W; Evelein, Annemieke M V; Fauser, Bart C J M; de Jager, Wilco

    2016-01-01

    To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Cross-sectional comparison of serum biomarkers. University Medical Center Utrecht. Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30). Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.

  11. Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure.

    Science.gov (United States)

    Bierer, Linda M; Bader, Heather N; Daskalakis, Nikolaos P; Lehrner, Amy L; Makotkine, Iouri; Seckl, Jonathan R; Yehuda, Rachel

    2014-10-01

    Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-h urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. The inverse association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the directional effect on offspring will

  12. A Novel Procedure for Rapid Imaging of Adult Mouse Brains with MicroCT Using Iodine-Based Contrast.

    Directory of Open Access Journals (Sweden)

    Ryan Anderson

    Full Text Available High-resolution Magnetic Resonance Imaging (MRI has been the primary modality for obtaining 3D cross-sectional anatomical information in animals for soft tissue, particularly brain. However, costs associated with MRI can be considerably high for large phenotypic screens for gross differences in the structure of the brain due to pathology and/or experimental manipulations. MicroCT (mCT, especially benchtop mCT, is becoming a common laboratory equipment with throughput rates equal or faster than any form of high-resolution MRI at lower costs. Here we explore adapting previously developed contrast based mCT to image adult mouse brains in-situ. We show that 2% weight per volume (w/v iodine-potassium iodide solution can be successfully used to image adult mouse brains within 48 hours post-mortem when a structural support matrix is used. We demonstrate that hydrogel can be effectively used as a perfusant which limits the tissue shrinkage due to iodine.

  13. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...

  14. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    OpenAIRE

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (...

  15. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

    Science.gov (United States)

    Kilpatrick, L A; Li, Q; Yang, J; Goddard, J C; Fekete, D M; Lang, H

    2011-06-01

    Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

  16. Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring.

    Science.gov (United States)

    Itzhak, Y; Ergui, I; Young, J I

    2015-02-01

    The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offspring behavior by disrupting epigenetic programming of gene expression in the brain. To simulate the human pattern of drug use, male and female C57Bl/6J mice were exposed to escalating doses of METH or saline from adolescence through adulthood; following mating, females continue to receive drug or saline through gestational day 17. F1 METH male offspring showed enhanced response to cocaine-conditioned reward and hyperlocomotion. Both F1 METH male and female offspring had reduced response to conditioned fear. Cross-fostering experiments have shown that certain behavioral phenotypes were modulated by maternal care of either METH or saline dams. Analysis of offspring hippocampal DNA methylation showed differentially methylated regions as a result of both METH in utero exposure and maternal care. Our results suggest that behavioral phenotypes and epigenotypes of offspring that were exposed to METH in utero are vulnerable to (a) METH exposure during embryonic development, a period when wide epigenetic reprogramming occurs, and (b) postnatal maternal care.

  17. Young offspring at genetic risk of adult psychoses: the form of the trajectory of IQ or memory may orient to the right dysfunction at the right time.

    Directory of Open Access Journals (Sweden)

    Michel Maziade

    2011-04-01

    Full Text Available Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations?In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members. We then identified 400 adult members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring (of an affected parent aged 7 to 22, who were administered a neuropsychological battery. We then constructed cross-sectional trajectories that were compared to those of controls.The childhood IQ deficit displayed a stability until young adulthood. The delay in visual memory exhibited a non-linear two-stage trajectory: a lagging period during childhood followed by a recuperation period from adolescence until adulthood, as supported by a significant Group x Age Periods interaction. No data suggested deterioration between 7 and 22.In these offspring at genetic risk, the developmental trajectory of global IQ impairment may not apply to specific domains of cognition such as episodic memory. Different cognitive dysfunctions would mark different developmental courses. The shape of the trajectories might itself have a meaning and provide empirical leads for targeting the right dysfunction at the right time in future prevention research.

  18. Exposure of pregnant rats to diverse chemicals during pregnancy causes elevated blood pressure in offspring

    Science.gov (United States)

    Objective: Global undernutrition, low protein diet or dexamethasone treatment during pregnancy has been demonstrated in animal models to result in adverse health effects including hypertension and insulln resistance in adult offspring. Most protocols that produce these effects ca...

  19. Wild jackdaws' reproductive success and their offspring's stress hormones are connected to provisioning rate and brood size, not to parental neophobia.

    Science.gov (United States)

    Greggor, Alison L; Spencer, Karen A; Clayton, Nicola S; Thornton, Alex

    2017-03-01

    Many species show individual variation in neophobia and stress hormones, but the causes and consequences of this variation in the wild are unclear. Variation in neophobia levels could affect the number of offspring animals produce, and more subtly influence the rearing environment and offspring development. Nutritional deficits during development can elevate levels of stress hormones that trigger long-term effects on learning, memory, and survival. Therefore measuring offspring stress hormone levels, such as corticosterone (CORT), helps determine if parental neophobia influences the condition and developmental trajectory of young. As a highly neophobic species, jackdaws (Corvus monedula) are excellent for exploring the potential effects of parental neophobia on developing offspring. We investigated if neophobic responses, alongside known drivers of fitness, influence nest success and offspring hormone responses in wild breeding jackdaws. Despite its consistency across the breeding season, and suggestions in the literature that it should have importance for reproductive fitness, parental neophobia did not predict nest success, provisioning rates or offspring hormone levels. Instead, sibling competition and poor parental care contributed to natural variation in stress responses. Parents with lower provisioning rates fledged fewer chicks, chicks from larger broods had elevated baseline CORT levels, and chicks with later hatching dates showed higher stress-induced CORT levels. Since CORT levels may influence the expression of adult neophobia, variation in juvenile stress responses could explain the development and maintenance of neophobic variation within the adult population. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats

    Science.gov (United States)

    Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be m...

  1. Effect of Perinatal Lead Exposure on the Social Behaviour of Laboratory Mice Offspring at Adolescent Age

    International Nuclear Information System (INIS)

    AbuTaweel Qasim M; Ajarem Jamaan S

    2008-01-01

    Lead ( Pb ) was given to Swiss-Webster female mice at the concentrations of 0.1 and 0.2% ( w/v ) , containing 550 and 1100 ppm of lead respectively, in their drinking water. Treatment started from day 1 of pregnancy until day 15 postnatally . Thereafter, the dams were switched to plain tap water. After the weaning period ( 21 days ), all male offspring were isolated (one animal per cage) for 14 days, and the isolated male offspring were subjected to 'Standard Opponenttest' at the age of 36 days . the results of this test showed a significant and dose-dependent increase in the non-social behaviour , whereas such results showed a significant decline in the social behaviour including naso-genital and naso-nasal contact, number of fights, rear, wall rear and displacement activities of the Pb exposed young adult male offspring. The present perinatal Pb effects in the male offspring are possibly via in utero exposure and/or via mother's milk. (author)

  2. Maternal Aerobic Exercise during Pregnancy Can Increase Spatial Learning by Affecting Leptin Expression on Offspring's Early and Late Period in Life Depending on Gender

    Directory of Open Access Journals (Sweden)

    Ayfer Dayi

    2012-01-01

    Full Text Available Maternal exercise during pregnancy has been suggested to exert beneficial effects on brain functions of the offspring. Leptin is an adipocytokine which is secreted from adipose tissues and has positive effects on learning, memory, and synaptic plasticity. In this study, pregnant rats were moderately exercised and we observed the effects of this aerobic exercise on their prepubertal and adult offsprings' spatial learning, hippocampal neurogenesis, and expression of leptin. All the pups whose mothers exercised during pregnancy learned the platform earlier and spent longer time in the target quadrant. Their thigmotaxis times were shorter than those measured in the control group. It is shown that hippocampal CA1, CA3 neuron numbers increased in both prepubertal and adult pups, in addition that GD neuron numbers increased in adult pups. Leptin receptor expression significantly increased in the prepubertal male, adult male, and adult female pups. In our study, maternal running during pregnancy resulted in significant increase in the expression of leptin receptor but not in prepubertal female pups, enhanced hippocampal cell survival, and improved learning memory capability in prepubertal and adult rat pups, as compared to the control group. In conclusion, maternal exercise during pregnancy may regulate spatial plasticity in the hippocampus of the offspring by increasing the expression of leptin.

  3. Impact of maternal mild hyperglycemia on maternal care and offspring development and behavior of Wistar rats.

    Science.gov (United States)

    Kiss, Ana Carolina Inhasz; Woodside, Barbara; Felício, Luciano Freitas; Anselmo-Franci, Janete; Damasceno, Débora Cristina

    2012-10-10

    The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Both high and low maternal salt intake in pregnancy alter kidney development in the offspring.

    Science.gov (United States)

    Koleganova, Nadezda; Piecha, Grzegorz; Ritz, Eberhard; Becker, Luis Eduardo; Müller, Annett; Weckbach, Monika; Nyengaard, Jens Randel; Schirmacher, Peter; Gross-Weissmann, Marie-Luise

    2011-08-01

    In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.

  5. Polyandry and fitness of offspring reared under varying nutritional stress in decorated crickets.

    Science.gov (United States)

    Sakaluk, Scott K; Schaus, Jennifer M; Eggert, Anne-Katrin; Snedden, W Andrew; Brady, Pamela L

    2002-10-01

    Females, by mating with more than one male in their lifetime, may reduce their risk of receiving sperm from genetically incompatible sires or increase their prospects of obtaining sperm from genetically superior sires. Although there is evidence of both kinds of genetic benefits in crickets, their relative importance remains unclear, and the extent to which experimentally manipulated levels of polyandry in the laboratory correspond to those that occur in nature remain unknown. We measured lifetime polyandry of free-living female decorated crickets, Gryllodes sigillatus, and conducted an experiment to determine whether polyandry leads to an increase in offspring viability. We experimentally manipulated both the levels of polyandry and opportunities for females to select among males, randomly allocating the offspring of experimental females to high-food-stress or low-food-stress regimes to complete their development. Females exhibited a high degree of polyandry, mating on average with more than seven different males during their lifetime and up to as many as 15. Polyandry had no effect on either the developmental time or survival of offspring. However, polyandrous females produced significantly heavier sons than those of monandrous females, although there was no difference in the adult mass of daughters. There was no significant interaction between mating treatment and offspring nutritional regimen in their effects on offspring mass, suggesting that benefits accruing to female polyandry are independent of the environment in which offspring develop. The sex difference in the extent to which male and female offspring benefit via their mother's polyandry may reflect possible differences in the fitness returns from sons and daughters. The larger mass gain shown by sons of polyandrous females probably leads to their increased reproductive success, either because of their increased success in sperm competition or because of their increased life span.

  6. Paternal B vitamin intake is a determinant of growth, hepatic lipid metabolism and intestinal tumor volume in female Apc1638N mouse offspring

    Science.gov (United States)

    Background: The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well. Objective: In the current study we sought to determine whether modulating pre-conception paternal B vitamin inta...

  7. The effect of maternal body condition score before and during pregnancy on the glucose tolerance of adult sheep offspring.

    Science.gov (United States)

    Cripps, Roselle L; Green, Lucy R; Thompson, John; Martin-Gronert, Malgorzata S; Monk, Melanie; Sheldon, I Martin; Hanson, Mark A; Hales, C N; Ozanne, Susan E

    2008-05-01

    This study investigates the effects of diet-induced changes in maternal body condition on glucose tolerance in sheep. Welsh Mountain ewes were established, by dietary manipulation, at a body condition score of 2 (lower body condition [LBCS], n = 17) or >3 (higher body condition [HBCS], n = 19) prior to and during pregnancy. Birth weight and postnatal growth were similar in LBCS and HBCS offspring. In young adulthood, LBCS offspring had increased fasting glucose levels (3.8 +/- 0.07 vs 3.6 +/- 0.05 mM, P < .05), poorer glucose tolerance (2274 +/- 22.6 vs 2161 +/- 33 min/mM, P < .01), and reduced insulin secretion (0.58 +/- 0.05 vs 0.71 +/- 0.07 nM/min, P = .07). Increased fasting glycemia, mild glucose intolerance, and impaired initial insulin secretory response, as observed in LBCS offspring, are indictors of increased diabetes risk in humans. These findings suggest that altered maternal body composition and an imbalance between the fetal and postnatal environment influence offspring glucose tolerance.

  8. Oligodendrocyte- and Neuron-Specific Nogo-A Restrict Dendritic Branching and Spine Density in the Adult Mouse Motor Cortex.

    Science.gov (United States)

    Zemmar, Ajmal; Chen, Chia-Chien; Weinmann, Oliver; Kast, Brigitt; Vajda, Flora; Bozeman, James; Isaad, Noel; Zuo, Yi; Schwab, Martin E

    2018-06-01

    Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO). We show that both oligodendrocyte- and neuron-specific Nogo-A KO mice have enhanced dendritic branching and spine densities in layer 2/3 cortical pyramidal neurons. These effects are compartmentalized: neuronal Nogo-A affects proximal dendrites whereas oligodendrocytic Nogo-A affects distal regions. Finally, we used two-photon laser scanning microscopy to measure the spine turnover rate of adult mouse motor cortex layer 5 cells and find that both Nogo-A KO mouse lines show enhanced spine remodeling after 4 days. Our results suggest relevant control functions of glial as well as neuronal Nogo-A for synaptic plasticity and open new possibilities for more selective and targeted plasticity enhancing strategies.

  9. Long-term influences of parental divorce on offspring affective disorders: A systematic review and meta-analysis.

    Science.gov (United States)

    Sands, Amy; Thompson, Ellen J; Gaysina, Darya

    2017-08-15

    The prevalence of divorce in Western countries has increased in recent decades. However, there is no recent systematic review and/or meta-analysis of studies testing for long-term effects of parental divorce on offspring affective disorders. The present study conducted a systematic review and meta-analysis of studies published since 1980 testing for the association between parental divorce and offspring depression and anxiety in adulthood. PUBMED, Science Direct, Medline, PsychInfo, and PsychArticles databases were searched for eligible studies. Random-effect meta-analyses were used to synthesize effect sizes and to test whether associations of parental divorce with offspring affective disorders differed among three publication periods (i.e., before 1996, 1996-2005, 2006-2015). In total, 29 studies were eligible for the systematic review, and 18 studies were included in the meta-analyses (depression: n=21,581; anxiety: n=2472). There was significant association between parental divorce and offspring depression (OR=1.56; 95%CI [1.31, 1.86]), but not anxiety (OR=1.16; 95%CI [0.98, 1.38]). The effect of parental divorce on offspring depression was not weaker in the reports published in more recent decades. There is limited research in relation to offspring anxiety in adulthood. Parental divorce is associated with an increased risk of adult offspring depression, with no indication of the effect being weaker in recent publications. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Transmission/disequilibrium tests incorporating unaffected offspring.

    Directory of Open Access Journals (Sweden)

    Qinyu Wei

    Full Text Available We propose a new method for family-based tests of association and linkage called transmission/disequilibrium tests incorporating unaffected offspring (TDTU. This new approach, constructed based on transmission/disequilibrium tests for quantitative traits (QTDT, provides a natural extension of the transmission/disequilibrium test (TDT to utilize transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. TDTU can be used in various study designs and can accommodate all types of independent nuclear families with at least one affected offspring. When the study sample contains only case-parent trios, the TDTU is equivalent to TDT. Informative-transmission disequilibrium test (i-TDT and generalized disequilibrium test(GDT are another two methods that can use information of both unaffected offspring and affected offspring. In contract to i-TDT and GDT, the test statistic of TDTU is simpler and more explicit, and can be implemented more easily. Through computer simulations, we demonstrate that power of the TDTU is slightly higher compared to i-TDT and GDT. All the three methods are more powerful than method that uses affected offspring only, suggesting that unaffected siblings also provide information about linkage and association.

  11. Plasticity of noddy parents and offspring to sea-surface temperature anomalies.

    Directory of Open Access Journals (Sweden)

    Carol A Devney

    Full Text Available Behavioral and/or developmental plasticity is crucial for resisting the impacts of environmental stressors. We investigated the plasticity of adult foraging behavior and chick development in an offshore foraging seabird, the black noddy (Anous minutus, during two breeding seasons. The first season had anomalously high sea-surface temperatures and 'low' prey availability, while the second was a season of below average sea-surface temperatures and 'normal' food availability. During the second season, supplementary feeding of chicks was used to manipulate offspring nutritional status in order to mimic conditions of high prey availability. When sea-surface temperatures were hotter than average, provisioning rates were significantly and negatively impacted at the day-to-day scale. Adults fed chicks during this low-food season smaller meals but at the same rate as chicks in the unfed treatment the following season. Supplementary feeding of chicks during the second season also resulted in delivery of smaller meals by adults, but did not influence feeding rate. Chick begging and parental responses to cessation of food supplementation suggested smaller meals fed to artificially supplemented chicks resulted from a decrease in chick demands associated with satiation, rather than adult behavioral responses to chick condition. During periods of low prey abundance, chicks maintained structural growth while sacrificing body condition and were unable to take advantage of periods of high prey abundance by increasing growth rates. These results suggest that this species expresses limited plasticity in provisioning behavior and offspring development. Consequently, responses to future changes in sea-surface temperature and other environmental variation may be limited.

  12. Investigation of genomic instability by assay of DNA fingerprint from the offspring of male mice exposed to chronic low-level γ-radiation

    International Nuclear Information System (INIS)

    Bezlepkin, V.G.; Vasil'eva, G.V.; Lomaeva, M.G.; Sirota, N.P.; Gaziev, A.I.

    2000-01-01

    By polymerase chain reaction with arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F 1 generation) from male parents of mice exposed to chronic low-dose γ-radiation was studied. Male mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old mice progeny for DNA separation. Primer in the AP-PCR was 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on chromosome 11 of the mouse. Comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of micro-satellite-associated sequences in the genome of the offspring of males exposed to 25 and 50 cGy. DNA-fingerprints of the offspring of male mice exposed to chronic irradiation doses 10 and 25 cGy. 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of non-parent bands. Result of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-dose radiation prior to fertilization [ru

  13. MRI visualization of endogenous neural progenitor cell migration along the RMS in the adult mouse brain

    DEFF Research Database (Denmark)

    Vreys, Ruth; Vande Velde, Greetje; Krylychkina, Olga

    2010-01-01

    The adult rodent brain contains neural progenitor cells (NPCs), generated in the subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS) towards the olfactory bulb (OB) where they differentiate into neurons. The aim of this study was to visualize endogenous NPC migration...... by a longitudinal MRI study and validated with histology. Here, we visualized endogenous NPC migration in the mouse brain by in vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time with ex vivo MRI. Furthermore, we investigated the influence of in situ injection of MPIOs on adult...

  14. Suicide and mental illness in parents and risk of suicide in offspring: a birth cohort study

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Wang, August G

    2009-01-01

    BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult...... the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4...

  15. Suicide and mental illness in parents and risk of suicide in offspring : A birth cohort study

    DEFF Research Database (Denmark)

    Sørensen, Holger; Mortensen, Erik Lykke; Wang, August

    2009-01-01

    BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult...... the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4...

  16. Offspring sex and parental health and mortality

    DEFF Research Database (Denmark)

    Næss, Øyvind; Mortensen, Laust H.; Vikanes, Åse

    2017-01-01

    ) number of total boy and girl offspring, 2) sex of the first and second offspring and 3) proportion of boys to total number of offspring. A sub-cohort (n = 50,736 mothers, n = 44,794 fathers) from survey data was analysed for risk factors. Mothers had increased risk of total and cardiovascular mortality...... that was consistent across approaches: cardiovascular mortality of 1.07 (95% CI: 1.03-1.11) per boy (approach 2), 1.04 (1.01-1.07) if the first offspring was a boy, and 1.06 (1.01-1.10) if the first two offspring were boys (approach 3). We found that sex of offspring was not associated with total or cardiovascular...

  17. Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

    Directory of Open Access Journals (Sweden)

    Golan Hava

    2004-04-01

    Full Text Available Abstract Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors.

  18. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

  19. Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors.

    Science.gov (United States)

    Groner, B; Hynes, N E

    1980-01-01

    The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257

  20. The influences of parental divorce and maternal-versus-paternal alcohol abuse on offspring lifetime suicide attempt.

    Science.gov (United States)

    Thompson, Ronald G; Alonzo, Dana; Hu, Mei-Chen; Hasin, Deborah S

    2017-05-01

    Research indicates that parental divorce and parental alcohol abuse independently increase likelihood of offspring lifetime suicide attempt. However, when experienced together, only parental alcohol abuse significantly increased odds of suicide attempt. It is unclear to what extent differences in the effect of maternal versus paternal alcohol use exist on adult offspring lifetime suicide attempt risk. This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime suicide attempt. The sample consisted of participants from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions. The simultaneous effect of childhood or adolescent parental divorce and maternal and paternal history of alcohol problems on offspring lifetime suicide attempt was estimated using a logistic regression model with an interaction term for demographics and parental history of other emotional and behavioural problems. Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime suicide attempt. Experiencing parental divorce and either maternal or paternal alcohol problems nearly doubled the likelihood of suicide attempt. Divorce and history of alcohol problems for both parents tripled the likelihood. Individuals who experienced parental divorce as children or adolescents and who have a parent who abuses alcohol are at elevated risk for lifetime suicide attempt. These problem areas should become a routine part of assessment to better identify those at risk for lifetime suicide attempt and to implement early and targeted intervention to decrease such risk. [Thompson RG Jr,Alonzo D, Hu M-C, Hasin DS. The influences of parental divorce and maternal-versus-paternal alcohol abuse on offspringlifetime suicide attempt. Drug Alcohol Rev 2017;36:408-414]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

  1. Subclinical inflammation during third trimester of pregnancy was not associated with markers of the metabolic syndrome in young adult offspring

    DEFF Research Database (Denmark)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte

    2014-01-01

    for maternal smoking during pregnancy, height, prepregnancy body mass index (BMI), education, and offspring's sex. Offspring MS markers included waist circumference, BMI, blood pressure, HOMA insulin resistance, and plasma levels of fasting glucose, triglycerides, cholesterol fractions, insulin, and leptin...

  2. Parental social networks during childhood and offspring depression in early adulthood: a lifecourse approach.

    Science.gov (United States)

    Allchin, Adelyn; Melchior, Maria; Fombonne, Eric; Surkan, Pamela J

    2016-07-04

    Little is known on how parental social relationships may affect their children's mental health. We sought to examine the relation between parental social relationship characteristics and subsequent offspring depression in young adulthood. We used 2009 Trajectoires Épidémiologiques en Population (TEMPO) study data from 1087 French young adults ages 22 to 35 and parental data from the corresponding Gaz et Eléctricité (GAZEL) study in 1991. Multivariable logistic regression was used to examine parental social networks, quality of parental relationships, and reciprocity of parental social support measured in 1991 in relation to offspring depression in young adulthood measured using the Adult Self Report in 2009. Analyses were stratified by participant sex. In adjusted models, daughters of parents who reported giving more support to others than they received had 1.72 higher odds (95% CI, 1.09-2.70) of depression in young adulthood. Daughters of parents who were unsatisfied with their social relationships had 2.14 (95% CI, 1.22-3.76) higher odds of depression. Among male participants, there was no statistically significant association between parental relationship satisfaction, reciprocity of parental exchanges, and depression. Parental relationships during mid-childhood have long-term associations with offspring depression. Results suggest that enhancing social support for parents may have positive implications for their children's mental health. © 2016 Wiley Periodicals, Inc.

  3. Latent profiles of nonresidential father engagement six years after divorce predict long-term offspring outcomes.

    Science.gov (United States)

    Modecki, Kathryn Lynn; Hagan, Melissa J; Sandler, Irwin; Wolchik, Sharlene A

    2015-01-01

    This study examined profiles of nonresidential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) 6 to 8 years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, 9 years later. Parental divorce occurred during late childhood to early adolescence; indicators of nonresidential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed 9 years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes 9 years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother's remarriage, mother's income, and gender, age, and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems 9 years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long term. Implications of findings for policy and intervention are discussed.

  4. Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of “Metabolic Memory”

    Directory of Open Access Journals (Sweden)

    Akadiri Yessoufou

    2011-01-01

    Full Text Available The adverse outcomes on the offspring from maternal diabetes in pregnancy are substantially documented. In this paper, we report main knowledge on impacts of maternal diabetes on early and long-term health of the offspring, with specific comments on maternal obesity. The main adverse outcome on progenies from pregnancy complicated with maternal diabetes appears to be macrosomia, as it is commonly known that intrauterine exposure to hyperglycemia increases the risk and programs the offspring to develop diabetes and/or obesity at adulthood. This “fetal programming”, due to intrauterine diabetic milieu, is termed as “metabolic memory”. In gestational diabetes as well as in macrosomia, the complications include metabolic abnormalities, degraded antioxidant status, disrupted immune system and potential metabolic syndrome in adult offspring. Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring's good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may be beneficial during both the pregnancy and offspring's future life.

  5. Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

    Science.gov (United States)

    Frihauf, Jennifer B; Fekete, Éva M; Nagy, Tim R; Levin, Barry E; Zorrilla, Eric P

    2016-12-01

    Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. Copyright © 2016 Frihauf et al.

  6. Evidence that a maternal "junk food" diet during pregnancy and lactation can reduce muscle force in offspring.

    Science.gov (United States)

    Bayol, Stéphanie A; Macharia, Raymond; Farrington, Samantha J; Simbi, Bigboy H; Stickland, Neil C

    2009-02-01

    Obesity is a multi-factorial condition generally attributed to an unbalanced diet and lack of exercise. Recent evidence suggests that maternal malnutrition during pregnancy and lactation can also contribute to the development of obesity in offspring. We have developed an animal model in rats to examine the effects of maternal overeating on a westernized "junk food" diet using palatable processed foods rich in fat, sugar and salt designed for human consumption. Using this model, we have shown that such a maternal diet can promote overeating and a greater preference for junk food in offspring at the end of adolescence. The maternal junk food diet also promoted adiposity and muscle atrophy at weaning. Impaired muscle development may permanently affect the function of this tissue including its ability to generate force. The aim of this study is to determine whether a maternal junk food diet can impair muscle force generation in offspring. Twitch and tetanic tensions were measured in offspring fed either chow alone (C) or with a junk food diet (J) during gestation, lactation and/or post-weaning up to the end of adolescence such that three groups of offspring were used, namely the CCC, JJC and JJJ groups. We show that adult offspring from mothers fed the junk food diet in pregnancy and lactation display reduced muscle force (both specific twitch and tetanic tensions) regardless of the post-weaning diet compared with offspring from mothers fed a balanced diet. Maternal malnutrition can influence muscle force production in offspring which may affect an individual's ability to exercise and thereby combat obesity.

  7. Alterations in offspring behavior induced by chronic prenatal cocaine dosing.

    Science.gov (United States)

    Smith, R F; Mattran, K M; Kurkjian, M F; Kurtz, S L

    1989-01-01

    Sperm-positive female Long-Evans hooded rats were dosed subcutaneously with 10 mg/kg/day cocaine or an equal volume of vehicle (0.9% sterile saline) from gestation day 4 (GD4) through GD18. Offspring were assessed for development of negative geotaxis, righting reflex, spontaneous alternation, and open field activity, and for adult behaviors including DRL-20 acquisition, water maze, visual discrimination, barbiturate sleep time, shuttlebox avoidance, footshock sensitivity, and tail flick latency. Cocaine dosing produced no significant effects on dam weight gain, any measure of litter size and weight, or early postnatal behavioral tests, but there were significant drug effects on development of spontaneous alternation, development of open field activity, DRL-20 acquisition, water maze performance, tail flick, and footshock sensitivity. These data suggest that chronic administration of a modest dose of cocaine during gestation in the rat alters a number of behaviors in the offspring.

  8. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  9. Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.

    Science.gov (United States)

    Vargas, Vladimir E; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M; Saunders, Debra; Njoku, Charity; Towner, Rheal; Myers, Dean A

    2017-01-01

    The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15-19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5-8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5-7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4-12 weeks of age fed a CD or HFD. By 14-23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.

  10. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

    Science.gov (United States)

    Canetta, S; Bolkan, S; Padilla-Coreano, N; Song, L J; Sahn, R; Harrison, N L; Gordon, J A; Brown, A; Kellendonk, C

    2016-07-01

    Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

  11. C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin.

    Directory of Open Access Journals (Sweden)

    John S House

    Full Text Available C/EBPalpha and C/EBPbeta are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPalpha and C/EBPbeta in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPalpha or C/EBPbeta alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPalpha and C/EBPbeta in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPalpha and C/EBPbeta in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3 and melanocortin 5 receptor (MC5R, two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPalpha and C/EBPbeta are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.

  12. Gender Difference in Offspring's Alcohol Use Disorder by 21 Years: A Longitudinal Study of Maternal Influences.

    Science.gov (United States)

    Tran, Nam T; Clavarino, Alexandra; Williams, Gail M; Najman, Jake M

    2018-04-16

    There is little known about the extent to which maternal alcohol consumption influences offspring's alcohol use disorder. This study aims to examine whether different maternal alcohol consumption trajectories predict gender difference in adolescent alcohol use disorder at child age 21 years. Data are from a prospective cohort, the Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes. The study involves 2531 mother-child pairs for whom data are available at the 21-year follow-up survey. Maternal alcohol consumption trajectories were determined by group-based trajectory modelling. Offspring's lifetime ever alcohol use disorder was assessed using DSM-IV diagnostic criteria. Over 14 years of follow-up after the birth of a child, three distinct alcohol consumption trajectories were identified (abstainer, low-stable. and moderate-escalating drinker). A maternal trajectory of moderate-escalating alcohol consumption independently predicted offspring's lifetime ever alcohol use disorder at 21 years after adjustment for a range of potential confounders. "Cross-gender influence" is observed in the study. A maternal life course pattern of alcohol consumption may have an independent effect on offspring alcohol consumption, with male offspring being more vulnerable to the effects of maternal alcohol use than are female offspring. Programs intended to address alcohol consumption by adolescents and young adults need to focus on the behaviors of both parents but acknowledging that maternal patterns of alcohol consumption may be particularly important for male offspring.

  13. Sex-specific effects of low-dose gestational estradiol-17β exposure on bone development in porcine offspring

    International Nuclear Information System (INIS)

    Flöter, Veronika L.; Galateanu, Gabriela; Fürst, Rainer W.; Seidlová-Wuttke, Dana; Wuttke, Wolfgang; Möstl, Erich; Hildebrandt, Thomas B.

    2016-01-01

    Highlights: • Sex-specific effects and non-monotonic dose responses were demonstrated after low-dose in utero E2 treatment in offspring. • Alterations in bone parameters were found in prepubertal male but not female offspring. • In postpubertal female offspring, cortical and total cross-sectional area were higher at the femoral midpoint. • In utero E2 treatment did neither significantly affect hormone concentrations nor puberty onset in offspring. • The results substantiate the high sensitivity of developing organisms to exogenous estrogens. - Abstract: Estrogens are important for the bone development and health. Exposure to endocrine disrupting chemicals during the early development has been shown to affect the bone phenotype later in life. Several studies have been performed in rodents, while in larger animals that are important to bridge the gap to humans there is a paucity of data. To this end, the pig as large animal model was used in the present study to assess the influence of gestational estradiol-17β (E2) exposure on the bone development of the prepubertal and adult offspring. Two low doses (0.05 and 10 μg E2/kg body weight) referring to the ‘acceptable daily intake’ (ADI) and the ‘no observed effect level’ (NOEL) as stated for humans, and a high-dose (1000 μg E2/kg body weight), respectively, were fed to the sows every day from insemination until delivery. In the male prepubertal offspring, the ADI dose group had a lower strength strain index (p = 0.002) at the proximal tibia compared to controls, which was determined by peripheral quantitative computed tomography. Prepubertal females were not significantly affected. However, there was a higher cortical cross-sectional area (CSA) (p = 0.03) and total CSA (p = 0.02) at the femur midpoint in the adult female offspring of the NOEL dose group as measured by computed tomography. These effects were independent from plasma hormone concentrations (leptin, IGF1, estrogens), which remained

  14. Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice.

    Science.gov (United States)

    Smarr, Benjamin L; Grant, Azure D; Perez, Luz; Zucker, Irving; Kriegsfeld, Lance J

    2017-06-12

    Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.

  15. Effects of the use of assisted reproduction and high-caloric diet consumption on body weight and cardiovascular health of juvenile mouse offspring.

    Science.gov (United States)

    Schenewerk, Angela L; Ramírez, Francisco Í; Foote, Christopher; Ji, Tieming; Martínez-Lemus, Luis A; Rivera, Rocío Melissa

    2014-01-01

    Maternal obesity and the use of assisted reproductive technologies (ART) are two suboptimal developmental environments that can lead to offspring obesity and cardiovascular disease. We hypothesized that these environments independently and synergistically adversely affect the offspring's weight and cardiovascular performance at ~7 weeks of age. Mice were fed either 24% fat and 17.5% high-fructose (HF) corn syrup or maintenance chow (5% fat; low-fat, no-fructose (LF)). Dams were subdivided into no ART and ART groups. ART embryos were cultured in Whitten's medium and transferred into pseudopregnant recipients consuming the same diet as the donor. Offspring were fed the same diet as the mother. Body weights (BW) were measured weekly and mean arterial pressure (MAP) was collected through carotid artery catheterization at killing (55±0.5 days old). Expression of genes involved in cardiovascular remodeling was measured in thoracic aorta using qRT-PCR, and levels of reactive oxygen species (ROS) were measured intracellularly and extracellularly in mesenteric resistance arteries. ART resulted in increased BW at weaning. This effect decreased over time and diet was the predominant determinant of BW by killing. Males had greater MAP than females (P=0.002) and HF consumption was associated with greater MAP regardless of sex (P<0.05). Gene expression was affected by sex (P<0.05) and diet (P<0.1). Lastly, the use of ART resulted in offspring with increased intracellular ROS (P=0.05). In summary, exposure to an obesogenic diet pre- and/or post-natally affects weight, MAP, and gene expression while ART increases oxidative stress in mesenteric resistance arteries of juvenile offspring, no synergistic effects were observed.

  16. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

    DEFF Research Database (Denmark)

    Gerstenberg, Marina Kjærgaard; Nilsson, C; Secher, A

    2017-01-01

    Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic...... for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling....... assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: P

  17. Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Li; Wu, Zhou; Baba, Masashi [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan); Peters, Christoph [Institute fuer Molekulare Medizin und Zellforshung, Albert-Ludwings-Universitaet Freiburg, D-79104 Freiburg (Germany); Uchiyama, Yasuo [Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo (Japan); Nakanishi, Hiroshi, E-mail: nakan@dent.kyushu-u.ac.jp [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan)

    2010-08-27

    Research highlights: {yields} Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. {yields} CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. {yields} CB-deficiency significantly increased the mean survival ratio of injured neurons. {yields} Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy

  18. Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

    International Nuclear Information System (INIS)

    Sun, Li; Wu, Zhou; Baba, Masashi; Peters, Christoph; Uchiyama, Yasuo; Nakanishi, Hiroshi

    2010-01-01

    Research highlights: → Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. → CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. → CB-deficiency significantly increased the mean survival ratio of injured neurons. → Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy-induced mortor neuron

  19. Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison.

    Science.gov (United States)

    Mesman, Esther; Birmaher, Boris B; Goldstein, Benjamin I; Goldstein, Tina; Derks, Eske M; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J; Reichart, Catrien G; Wals, Marjolein; Verhulst, Frank C; Nolen, Willem A; Hillegers, Manon H J

    2016-11-15

    Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, ppsychopathology based on CBCL reports. Preliminary measure of inter-site reliability. We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison✩

    Science.gov (United States)

    Mesman, Esther; Birmaher, Boris B.; Goldstein, Benjamin I.; Goldstein, Tina; Derks, Eske M.; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J.; Reichart, Catrien G.; Wals, Marjolein; Verhulst, Frank C.; Nolen, Willem A.; Hillegers, Manon H.J.

    2017-01-01

    Objective Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. Methods We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10–18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Results Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, ppsychopathology based on CBCL reports. Limitations Preliminary measure of inter-site reliability. Conclusions We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. PMID:27423424

  1. Latent profiles of non-residential father engagement six years after divorce predict long term offspring outcomes

    Science.gov (United States)

    Modecki, Kathryn Lynn; Hagan, Melissa; Sandler, Irwin; Wolchik, Sharlene

    2014-01-01

    This study examined profiles of non-residential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) six to eight years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, nine years later. Parental divorce occurred during late childhood to early adolescence; indicators of non-residential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed nine years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes nine years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother’s remarriage, mother’s income, and gender, age and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems nine years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long-term. Implications of findings for policy and intervention are discussed. PMID:24484456

  2. Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus

    OpenAIRE

    Smalheiser, Neil R; Lugli, Giovanni; Lenon, Angela L; Davis, John M; Torvik, Vetle I; Larson, John

    2010-01-01

    Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct respon...

  3. Strain preservation of experimental animals: vitrification of two-cell stage embryos for multiple mouse strains.

    Science.gov (United States)

    Eto, Tomoo; Takahashi, Riichi; Kamisako, Tsutomu

    2015-04-01

    Strain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3-33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Low-grade inflammation in young adults exposed to intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Clausen, Tine Dalsgaard; Mathiesen, Elisabeth R

    2012-01-01

    AIM: To investigate associations between fetal exposure to intrauterine hyperglycemia and plasma concentrations of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in adult offspring. METHOD: We studied 597 offspring, aged 18-27years, from four different groups concerning...

  5. Parental Educational Attainment and Offspring Subjective Well-being and Self-Beliefs in Older Adulthood.

    Science.gov (United States)

    Sutin, Angelina R; Stephan, Yannick; Terracciano, Antonio

    2018-07-01

    This research examines whether parental educational attainment and subjective childhood socioeconomic status (SES) is associated with adult offspring well-being and self-beliefs (broadly defined). Participants from the Health and Retirement Study were included if they completed the leave-behind questionnaire in 2006 or 2008 ( N =10,827; M age =68.38; SD =9.81; range=50-101). Participants reported on their own and both parents educational attainment, subjective childhood financial situation, and financial difficulties in childhood at study entry and on well-being in 2006/2008. Linear regression was used to examine the association between offspring education, parental education, childhood SES and three aspects of well-being and self-beliefs: positive affect (e.g., positive emotions, optimism), negative affect (e.g., loneliness, hostility), and cognitive evaluation (e.g., life satisfaction). Participants with more education reported higher well-being (median β=.12). Parental educational attainment, subjective childhood SES, and a significant financial event during childhood were associated with more positive affect, less negative affect, and higher life satisfaction (median β=.05); these associations held controlling for offspring education. The educational and financial environment of childhood may hamper well-being into older adulthood; the offspring's own experiences and achievements do not completely attenuate the association with these aspects of the childhood environment.

  6. The effect of offspring on depressive disorder among old adults: Evidence from the Korean Longitudinal Study of Aging from 2006 to 2012.

    Science.gov (United States)

    Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Choi, Young; Park, Eun-Cheol

    2015-01-01

    To investigate whether having an offspring protects against or increases the risk of depressive disorders. Data from the Korean Longitudinal Study of Aging (KLoSA) from 2006 and 2012 was assessed using longitudinal data analysis. We have included 10,149 research subjects at baseline and estimated the prevalence of depressive disorders for those with children. The number of offspring was from zero to five or more, and the composition of offspring is from zero boys and zero girls to two or more boys and two or more girls. For parents with zero offspring, the estimate for depressive disorder was 0.464 higher (SE: 0.123, p-value: 0.000, OR: 1.389; 95% CI: 1.176-1.640) and for parents with five or more offspring, the estimate for depressive disorder was 0.1 higher (SE: 0.104, p-value: 0.013, OR: 1.315; 95% CI: 1.150-1.504) compared to parents with two offspring. For parents with zero boys and zero girls, the estimate for depressive disorder was 0.599 higher (SE: 4.750, p-value: depressive disorder was 1.328 higher (SE: 3.820, p-value: 0.000, OR: 1.328; 95% CI: 1.189-1.482) compared to parents with one boy and one girl. Our results indicate that there is a large effect of offspring on the prevalence of depressive disorder, with significant positive effects for mothers. Fathers are at lower risk for depressive disorder than mothers, and the graph was U-shaped. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. The role of maternal early-life and later-life risk factors on offspring low birth weight: findings from a three-generational study.

    Science.gov (United States)

    Gavin, Amelia R; Hill, Karl G; Hawkins, J David; Maas, Carl

    2011-08-01

    This study examined three research questions: (1) Is there an association between maternal early-life economic disadvantage and the birth weight of later-born offspring? (2) Is there an association between maternal abuse in childhood and the birth weight of later-born offspring? (3) To what extent are these early-life risks mediated through adolescent and adult substance use, mental and physical health status, and adult socioeconomic status (SES)? Analyses used structural equation modeling to examine data from two longitudinal studies, which included three generations. The first generation (G1) and the second generation (G2) were enrolled in the Seattle Social Development Project (SSDP), and the third generation (G3) was enrolled in the SSDP Intergenerational Project. Data for the study (N = 136) focused on (G2) mothers enrolled in the SSDP and their children (G3). Analyses revealed that G2 low childhood SES predicted G3 offspring birth weight. Early childhood abuse among G2 respondents predicted G3 offspring birth weight through a mediated pathway including G2 adolescent substance use and G2 prenatal substance use. Birth weight was unrelated to maternal adult SES, depression, or obesity. To our knowledge, this is the first study to identify the effect of maternal early-life risks of low childhood SES and child maltreatment on later-born offspring birth weight. These findings have far-reaching effects on the cumulative risk associated with early-life economic disadvantage and childhood maltreatment. Such findings encourage policies and interventions that enhance child health at birth by taking the mother's own early-life and development into account. Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  8. Is the association between offspring intelligence and parents' educational attainment influenced by schizophrenia or mood disorder in parents?

    Directory of Open Access Journals (Sweden)

    Aja Neergaard Greve

    2017-09-01

    Full Text Available Results from twin, family, and adoption studies all suggest that general intelligence is highly heritable. Several studies have shown lower premorbid intelligence in individuals before the onset of both mood disorders and psychosis, as well as in children and adolescents at genetic high risk for developing schizophrenia. Based on these findings, we aim to investigate if the association between educational achievement in parents and intelligence in their offspring is influenced by schizophrenia or mood disorder in parents. In a large population-based sample of young adult male conscripts (n = 156,531 the presence of a mental disorder in the parents were associated with significantly lower offspring scores on a test of general intelligence, the Børge Priens Prøve (BPP, and higher educational attainment in parents was significantly associated with higher BPP test scores in offspring. A significant interaction suggested that the positive association between maternal education and offspring intelligence was stronger in offspring of mothers with schizophrenia compared to the control group (p = 0.03. The associations between parental education and offspring intelligence are also observed when restricting the sample to conscripts whose parents are diagnosed after 30 years of age. In conclusion, findings from this study show a more positive effect of education on offspring intelligence in mothers with schizophrenia compared to mothers from the control group. This effect could have both environmental and genetic explanations.

  9. Rats treated with Hypericum perforatum during pregnancy generate offspring with behavioral changes in adulthood

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    Leandro V. Campos

    Full Text Available Abstract Drugs used in the treatment of depression can cross the placenta giving rise to questions regarding the effects these drugs exert on the fetus. Hypericum perforatum L., Hypericaceae, is a natural product used to treat depression. However, information about its toxicity and the occurrence of alterations in the central nervous system development of the offspring is scarce. This work assessed the behavior of adult male rats born from mothers treated with Hypericum extract during gestation and analyzed the fluorescence of the extract in different organs of mothers and fetuses. Male pups were divided into three treated groups, corresponding to the administration of the Hypericum extract to mothers at the dose levels of 36 mg/kg, 72 mg/kg and 144 mg/kg, and one control group in which the mothers received distilled water. At 90 days of age, the offspring underwent the following tests: rotarod, pentobarbital-induced sleep time, elevated plus maze, hole-board and forced swimming test. The observed fluorescence indicated the presence of the extract in all tissues analyzed. The obtained results suggest lasting changes in the performances displayed in the CNS, depression and anxiety tests, indicating that the use of Hypericum during gestation could interfere with the behavioral development of the offspring reducing anxiety and depression when they become adults. We suggest that these alterations are associated with the reprogramming of the brain regions related to changes in emotional reactivity.

  10. Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls.

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    Cristina Solé-Padullés

    Full Text Available Schizophrenia (SZ and bipolar disorder (BD share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27, offspring of patients with BD (N = 39 and offspring of community control parents (N = 40. We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

  11. THE SOCIAL ENVIRONMENT AND NEUROGENESIS IN THE ADULT MAMMALIAN BRAIN

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    Claudia eLieberwirth

    2012-05-01

    Full Text Available Adult neurogenesis—the formation of new neurons in adulthood—has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones as well as exogenous (e.g., physical activity and environmental complexity factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. Most recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult-adult (e.g., mating, conspecific, and chemosensory signal exposure and adult-offspring (e.g., gestation, parenthood, and exposure to offspring interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant-subordinate interactions on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed.

  12. Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner

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    Simon Lecoutre

    2017-08-01

    Conclusions: Consistent with the DOHaD hypothesis, persistent epigenetic remodeling occurs at regulatory regions especially within intergenic sequences, linked to higher leptin gene expression in adult HF offspring in a depot-specific manner.

  13. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

    Science.gov (United States)

    Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid...

  14. Doublecortin (DCX is not essential for survival and differentiation of newborn neurons in the adult mouse dentate gyrus

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    Jagroop eDhaliwal

    2016-01-01

    Full Text Available In the adult brain, expression of the microtubule-associated protein Doublecortin (DCX is associated with neural progenitor cells (NPCs that give rise to new neurons in the dentate gyrus. Many studies quantify the number of DCX-expressing cells as a proxy for the level of adult neurogenesis, yet no study has determined the effect of removing DCX from adult hippocampal NPCs. Here, we use a retroviral and inducible mouse transgenic approach to either knockdown or knockout DCX from adult NPCs in the dentate gyrus and examine how this affects cell survival and neuronal maturation. Our results demonstrate that shRNA-mediated knockdown of DCX or Cre-mediated recombination in floxed DCX mice does not alter hippocampal neurogenesis and does not change the neuronal fate of the NPCs. Together these findings show that the survival and maturation of adult-generated hippocampal neurons does not require DCX.

  15. Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

    Science.gov (United States)

    Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

    2018-05-05

    Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. PPARg mRNA in the adult mouse hypothalamus: distribution and regulation in response to dietary challenges

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    Yang eLiu

    2015-09-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARg is a ligand-activated transcription factor that was originally identified as a regulator of peroxisome proliferation and adipocyte differentiation. Emerging evidence suggests that functional PPARg signaling also occurs within the hypothalamus. However, the exact distribution and identities of PPARg-expressing hypothalamic cells remains under debate. The present study systematically mapped PPARg mRNA expression in the adult mouse brain using in situ hybridization histochemistry. PPARg mRNA was found to be expressed at high levels outside the hypothalamus including the neocortex, the olfactory bulb, the organ of the vasculosum of the lamina terminalis, and the subfornical organ. Within the hypothalamus, PPARg was present at moderate levels in the suprachiasmatic nucleus and the ependymal of the 3rd ventricle. In all examined feeding-related hypothalamic nuclei, PPARg was expressed at very low levels that were close to the limit of detection. Using qPCR techniques, we demonstrated that PPARg mRNA expression was upregulated in the suprachiasmatic nucleus in response to fasting. Double in situ hybridization further demonstrated that PPARg was primarily expressed in neurons. Collectively, our observations provide a comprehensive map of PPARg distribution and regulation in the intact adult mouse hypothalamus.

  17. Radiation risk of individual multifactorial diseases in offspring of the atomic-bomb survivors: a clinical health study

    International Nuclear Information System (INIS)

    Tatsukawa, Yoshimi; Yamada, Michiko; Ohishi, Waka; Hida, Ayumi; Akahoshi, Masazumi; Fujiwara, Saeko; Cologne, John B; Hsu, Wan-Ling; Furukawa, Kyoji; Takahashi, Norio; Nakamura, Nori; Suyama, Akihiko; Ozasa, Kotaro; Shore, Roy

    2013-01-01

    There is no convincing evidence regarding radiation-induced heritable risks of adult-onset multifactorial diseases in humans, although it is important from the standpoint of protection and management of populations exposed to radiation. The objective of the present study was to examine whether parental exposure to atomic-bomb (A-bomb) radiation led to an increased risk of common polygenic, multifactorial diseases—hypertension, hypercholesterolaemia, diabetes mellitus, angina pectoris, myocardial infarction or stroke—in the first-generation (F 1 ) offspring of A-bomb survivors. A total of 11 951 F 1 offspring of survivors in Hiroshima or Nagasaki, conceived after the bombing, underwent health examinations to assess disease prevalence. We found no evidence that paternal or maternal A-bomb radiation dose, or the sum of their doses, was associated with an increased risk of any multifactorial diseases in either male or female offspring. None of the 18 radiation dose–response slopes, adjusted for other risk factors for the diseases, was statistically significantly elevated. However, the study population is still in mid-life (mean age 48.6 years), and will express much of its multifactorial disease incidence in the future, so ongoing longitudinal follow-up will provide increasingly informative risk estimates regarding hereditary genetic effects for incidence of adult-onset multifactorial disease. (paper)

  18. Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

    Science.gov (United States)

    Smith, B L; Reyes, T M

    2017-10-01

    Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Windscapes shape seabird instantaneous energy costs but adult behavior buffers impact on offspring.

    Science.gov (United States)

    Elliott, Kyle Hamish; Chivers, Lorraine S; Bessey, Lauren; Gaston, Anthony J; Hatch, Scott A; Kato, Akiko; Osborne, Orla; Ropert-Coudert, Yan; Speakman, John R; Hare, James F

    2014-01-01

    Windscapes affect energy costs for flying animals, but animals can adjust their behavior to accommodate wind-induced energy costs. Theory predicts that flying animals should decrease air speed to compensate for increased tailwind speed and increase air speed to compensate for increased crosswind speed. In addition, animals are expected to vary their foraging effort in time and space to maximize energy efficiency across variable windscapes. We examined the influence of wind on seabird (thick-billed murre Uria lomvia and black-legged kittiwake Rissa tridactyla) foraging behavior. Airspeed and mechanical flight costs (dynamic body acceleration and wing beat frequency) increased with headwind speed during commuting flights. As predicted, birds adjusted their airspeed to compensate for crosswinds and to reduce the effect of a headwind, but they could not completely compensate for the latter. As we were able to account for the effect of sampling frequency and wind speed, we accurately estimated commuting flight speed with no wind as 16.6 ms(?1) (murres) and 10.6 ms(?1) (kittiwakes). High winds decreased delivery rates of schooling fish (murres), energy (murres) and food (kittiwakes) but did not impact daily energy expenditure or chick growth rates. During high winds, murres switched from feeding their offspring with schooling fish, which required substantial above-water searching, to amphipods, which required less above-water searching. Adults buffered the adverse effect of high winds on chick growth rates by switching to other food sources during windy days or increasing food delivery rates when weather improved.

  20. Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

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    Tsolova Svetla

    2009-04-01

    Full Text Available Abstract Background Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN is usually considered a non-inflammatory disease. Methods We examined a marker of inflammation, C-reactive protein (CRP, in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models. Results Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only, serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function. Conclusion Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.

  1. Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle.

    Science.gov (United States)

    Kapoor, Amita; Matthews, Stephen G

    2008-12-01

    Prenatal stress is associated with altered behavior and hypothalamic-pituitary-adrenal (HPA) axis function postnatally. Recent studies suggest that these outcomes are dependent on the timing of the prenatal stress. The majority of these studies have been carried out in male offspring. We hypothesized that a short period of prenatal stress would result in female offspring that exhibit differences in open-field behavior and HPA axis activity, but the outcome would depend on the timing of the prenatal stress and the stage of the reproductive cycle. Pregnant guinea pigs were exposed to a strobe light during the fetal brain growth spurt [gestational d 50-52 (PS50)] or during the period of rapid brain myelination [gestational d 60-62 (PS60)]. Open-field activity was assessed in juvenile and adult female offspring. HPA axis function was tested in adult offspring. All tests in adulthood were carried out during the estrous and luteal phases of the reproductive cycle to determine the effect of stage on HPA axis programming. Tissues were collected upon completion of the study for analysis by in situ hybridization. PS60 offspring exhibited decreased activity in an open field during the estrous phase of the reproductive cycle compared with control offspring. Both PS50 and PS60 offspring exhibited a lower salivary cortisol response to a stressor, only during the estrous phase. Consistent with the behavioral and endocrine data, PS60 females exhibited lower plasma estradiol levels, reduced ovary weight, and increased glucocorticoid receptor mRNA in the paraventricular nucleus. In conclusion, we have demonstrated that there are effects of prenatal stress on behavior and HPA axis functioning in female offspring but that the outcomes are dependent on the timing of the prenatal stress together with the status of the reproductive cycle.

  2. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring.

    Science.gov (United States)

    Yehuda, Rachel; Daskalakis, Nikolaos P; Lehrner, Amy; Desarnaud, Frank; Bader, Heather N; Makotkine, Iouri; Flory, Janine D; Bierer, Linda M; Meaney, Michael J

    2014-08-01

    Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor (GR-1F) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring. Adult offspring with at least one Holocaust survivor parent (N=80) and demographically similar participants without parental Holocaust exposure or parental PTSD (N=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of GR-1F promoter methylation and of cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical clustering analysis was used to permit visualization of maternal compared with paternal PTSD effects on clinical variables and GR-1F promoter methylation. A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1F promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1F promoter methylation was significantly associated with greater postdexamethasone cortisol suppression. The clustering analysis revealed that maternal and paternal PTSD effects were differentially associated with clinical indicators and GR-1F promoter methylation. This is the first study to demonstrate alterations of GR-1F promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities.

  3. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice

    OpenAIRE

    Balsevich, G.; Baumann, V.; Uribe, A.; Chen, A.; Schmidt, M.

    2016-01-01

    Background: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. Methods: We used a mouse...

  4. Sex roles, parental care and offspring growth in two contrasting coucal species.

    Science.gov (United States)

    Goymann, Wolfgang; Safari, Ignas; Muck, Christina; Schwabl, Ingrid

    2016-10-01

    The decision to provide parental care is often associated with trade-offs, because resources allocated to parental care typically cannot be invested in self-maintenance or mating. In most animals, females provide more parental care than males, but the reason for this pattern is still debated in evolutionary ecology. To better understand sex differences in parental care and its consequences, we need to study closely related species where the sexes differ in offspring care. We investigated parental care in relation to offspring growth in two closely related coucal species that fundamentally differ in sex roles and parental care, but live in the same food-rich habitat with a benign climate and have a similar breeding phenology. Incubation patterns differed and uniparental male black coucals fed their offspring two times more often than female and male white-browed coucals combined. Also, white-browed coucals had more 'off-times' than male black coucals, during which they perched and preened. However, these differences in parental care were not reflected in offspring growth, probably because white-browed coucals fed their nestlings a larger proportion of frogs than insects. A food-rich habitat with a benign climate may be a necessary, but-perhaps unsurprisingly-is not a sufficient factor for the evolution of uniparental care. In combination with previous results (Goymann et al . 2015 J. Evol. Biol . 28 , 1335-1353 (doi:10.1111/jeb.12657)), these data suggest that white-browed coucals may cooperate in parental care, because they lack opportunities to become polygamous rather than because both parents were needed to successfully raise all offspring. Our case study supports recent theory suggesting that permissive environmental conditions in combination with a particular life history may induce sexual selection in females. A positive feedback loop among sexual selection, body size and adult sex-ratio may then stabilize reversed sex roles in competition and parental care.

  5. Problem partners and parenting: exploring linkages with maternal insecure attachment style and adolescent offspring internalizing disorder.

    Science.gov (United States)

    Bifulco, Antonia; Moran, Patricia; Jacobs, Catherine; Bunn, Amanda

    2009-01-01

    An intergenerational study examined mothers' insecure attachment style using the Attachment Style Interview (ASI; Bifulco et al., 2002a) in relation to her history of partner relationships, her parenting competence, and depression or anxiety disorder in her offspring. The sample comprised 146 high-risk, mother-adolescent offspring pairs in London, who were recruited on the basis of the mothers' psychosocial vulnerability for depression. Retrospective, biographical, and clinical interviews were undertaken independently with mother and offspring. A path model was developed, which showed that mothers' insecure attachment style had no direct link to either recalled child neglect/abuse or currently assessed disorder in their adolescent and young adult offspring. The connections appeared to be indirect, through the quality of relationships in the family system: mothers' insecure attachment and their partners' problem behavior accounted for variance in mothers' incompetent parenting as rated by interviewers. These variables predicted her neglect/abuse of the child, which was the only variable directly associated with internalizing disorder in her offspring. Mother's lifetime depression did not add to the model. It is argued that an ecological approach (emphasizing social adversity and different role domains) and a lifespan approach (emphasizing a history of adverse relationships a different life stages) is important in understanding the mechanisms by which parental insecure attachment style influences transmission of risk to the next generation.

  6. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    Science.gov (United States)

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  7. Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring.

    Directory of Open Access Journals (Sweden)

    Randy F Crossland

    Full Text Available Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP or a control protein (20% protein, C diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein and single-housed until 8-12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration, depression (tail suspension and forced swim test, sociability (three-chamber, repetitive (marble burying, learning and memory (fear conditioning, and circadian behavior (wheel-running activity during light-dark and constant dark cycles. We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT. Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03, less energy expenditure (P = 0.004, less rearing activity (P = 0.04 and a greater number of night-time rest/sleep bouts (P = 0.03 compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01 but had no learning and memory deficit in fear-conditioning assay (P = 0.02. There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces

  8. The psychological, social, and behavioural impact of a parent's cancer on adolescent and young adult offspring aged 10-24 at time of diagnosis: A systematic review.

    Science.gov (United States)

    Morris, Julia; Turnbull, Deborah; Preen, David; Zajac, Ian; Martini, Angelita

    2018-06-01

    This study reviewed the literature regarding the psychological, social, and behavioural impact of parental cancer on offspring aged 10-24 years, at the time of the parent's first diagnosis. A systematic literature review was conducted following 2015 PRISMA guidelines. Seven studies met inclusion criteria. Offspring were impacted by their parent's cancer and experienced psychological and behavioural problems. Daughters and offspring who experienced more problems at their parent's diagnosis appeared to be most impacted. Offspring refrained from communicating their disease-related concerns, but expected their parents to communicate openly. Turning to oneself and peer-support were coping strategies used by offspring. The majority of offspring were significantly impacted by their parent's cancer. The paucity of literature focusing on offspring aged 10-24 years at the time of their parent's incident cancer diagnosis indicates that research has overlooked offspring age at their parent's cancer onset as a factor that may influence their future outcomes. Copyright © 2018. Published by Elsevier Ltd.

  9. In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells.

    Science.gov (United States)

    Ishikura, Yukiko; Yabuta, Yukihiro; Ohta, Hiroshi; Hayashi, Katsuhiko; Nakamura, Tomonori; Okamoto, Ikuhiro; Yamamoto, Takuya; Kurimoto, Kazuki; Shirane, Kenjiro; Sasaki, Hiroyuki; Saitou, Mitinori

    2016-12-06

    The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR γ methylation in offspring, grand-offspring mice.

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    Zhonghai Yan

    Full Text Available Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear.We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected.Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR γ, CCAAT/enhancer-binding proteins (C/EBP α, cyclooxygenase (Cox-2, fatty acid synthase (FAS and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue.Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice.Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.

  11. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis.

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    Diane Rebourcet

    Full Text Available The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

  12. The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.

    Science.gov (United States)

    Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia; Najman, Jake

    2014-01-01

    Cross-sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20 years, and completed a questionnaire about their own depressive symptoms 2 to 5 years later. Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Poor physical health in early childhood and its effects on young adults' social functioning and levels of health related stress is one important pathway by which maternal depression has long-term consequences for offspring mental health. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  13. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

    2016-11-01

    Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Protein composition and synthesis in the adult mouse spinal cord

    International Nuclear Information System (INIS)

    Stodieck, L.S.; Luttges, M.W.

    1983-01-01

    Properties of spinal cord proteins were studied in adult mice subjected to unilateral crush or electrical stimulation of sciatic nerve. The protein composition of spinal tissue was determined using SDS-polyacrylamide gel electrophoresis coupled with subcellular fractionation. Comparisons of mouse spinal cord and brain revealed similarities in the types but differences in the concentrations of myelin associated proteins, nuclear histones and other proteins. Comparisons with sciatic nerve proteins demonstrated differences in types of proteins but similarities in the concentration of myelin proteins and nuclear histones. The short term (less than 2 hrs.) incorporation of radioactive amino acids into spinal cord proteins revealed heterogeneous rates of incorporation. Neither nerve crush six days prior to testing nor sciatic nerve stimulation had a significant effect on the protein composition or amino acid incorporation rates of spinal cord tissue. These observations suggest that known differences in spinal cord function following alterations in nerve input may be dependent upon different mechanisms than have been found in the brain

  15. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

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    Nadine M P Daan

    Full Text Available To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.Cross-sectional comparison of serum biomarkers.University Medical Center Utrecht.Hyperandrogenic PCOS women (HA-PCOS, n = 34, normoandrogenic PCOS women (NA-PCOS, n = 34, non-PCOS reference population (n = 32, PCOS offspring (n = 14, age 6-8 years, and a paedriatic reference population (n = 30.Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1, growth factors (PIGF, VEGF, sVEGF-R1, soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106, and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S. Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100.The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219 and adiponectin (R2 = 0.182 showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001, DPP-IV (P = 0.005, and adiponectin (P < 0.001. Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001 and S100A8 (P < 0.001 concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers

  16. Consequences of gestational diabetes to the brain and behavior of the offspring

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    RICARDO A.L. DE SOUSA

    2017-08-01

    Full Text Available ABSTRACT Gestational diabetes mellitus (GD is a form of insulin resistance triggered during the second/third trimesters of pregnancy in previously normoglycemic women. It is currently estimated that 10% of all pregnancies in the United States show this condition. For many years, the transient nature of GD has led researchers and physicians to assume that long-term consequences were absent. However, GD diagnosis leads to a six-fold increase in the risk of developing type 2 diabetes (T2D in women and incidence of obesity and T2D is also higher among their infants. Recent and concerning evidences point to detrimental effects of GD on the behavior and cognition of the offspring, which often persist until adolescence or adulthood. Considering that the perinatal period is critical for determination of adult behavior, it is expected that the intra-uterine exposure to hyperglycemia, hyperinsulinemia and pro-inflammatory mediators, hallmark features of GD, might affect brain development. Here, we review early clinical and experimental evidence linking GD to consequences on the behavior of the offspring, focusing on memory and mood disorders. We also discuss initial evidence suggesting that downregulation of insulin signaling cascades are seen in the brains of GD offspring and could contribute to the consequences on their behavior.

  17. Low offspring survival in mountain pine beetle infesting the resistant Great Basin bristlecone pine supports the preference-performance hypothesis.

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    Erika L Eidson

    Full Text Available The preference-performance hypothesis states that ovipositing phytophagous insects will select host plants that are well-suited for their offspring and avoid host plants that do not support offspring performance (survival, development and fitness. The mountain pine beetle (Dendroctonus ponderosae, a native insect herbivore in western North America, can successfully attack and reproduce in most species of Pinus throughout its native range. However, mountain pine beetles avoid attacking Great Basin bristlecone pine (Pinus longaeva, despite recent climate-driven increases in mountain pine beetle populations at the high elevations where Great Basin bristlecone pine grows. Low preference for a potential host plant species may not persist if the plant supports favorable insect offspring performance, and Great Basin bristlecone pine suitability for mountain pine beetle offspring performance is unclear. We infested cut bolts of Great Basin bristlecone pine and two susceptible host tree species, limber (P. flexilis and lodgepole (P. contorta pines with adult mountain pine beetles and compared offspring performance. To investigate the potential for variation in offspring performance among mountain pine beetles from different areas, we tested beetles from geographically-separated populations within and outside the current range of Great Basin bristlecone pine. Although mountain pine beetles constructed galleries and laid viable eggs in all three tree species, extremely few offspring emerged from Great Basin bristlecone pine, regardless of the beetle population. Our observed low offspring performance in Great Basin bristlecone pine corresponds with previously documented low mountain pine beetle attack preference. A low preference-low performance relationship suggests that Great Basin bristlecone pine resistance to mountain pine beetle is likely to be retained through climate-driven high-elevation mountain pine beetle outbreaks.

  18. Trajectories of maternal leisure-time physical activity and sedentary behavior during adolescence to young adulthood and offspring birthweight.

    Science.gov (United States)

    Badon, Sylvia E; Littman, Alyson J; Chan, Kwun Chuen Gary; Williams, Michelle A; Enquobahrie, Daniel A

    2017-11-01

    The objectives of the study were to determine the extent to which trajectories of maternal preconception leisure-time physical activity (LTPA) and leisure-time sedentary behavior (LTSB) during adolescence and young adulthood are associated with offspring birth weight (BW) and to test if these associations differ by offspring sex or maternal pre-pregnancy overweight-obese status. Participants with one or more birth (n = 1408) were identified from the National Longitudinal Study of Adolescent to Adult Health. Group-based trajectory modeling was used to characterize trajectories of LTPA (frequency/week) and LTSB (hours/week) which were measured, on average, over 7 years between age 15 and 22 years. Weighted regression and Wald tests were used to estimate and test mean differences and odds ratios for BW, small for gestational age, and large for gestational age (LGA). Three trajectories were identified for LTPA and five for LTSB. Associations differed by offspring sex for continuous BW and LGA (interaction P = .10 and .008, respectively). Among female offspring, participants with high followed by decreasing LTPA delivered offspring with 90 g greater BW (95% confidence interval [CI]: -4 to 184) and 72% greater risk of LGA (95% CI: 0.94-3.14), compared with participants with low LTPA. Among male offspring, LTPA patterns were not associated with BW. A pattern of high then decreasing LTPA among normal weight, but not overweight-obese women, was associated with 2.03 times greater risk of LGA (95% CI: 1.06-3.88). LTSB trajectories were not associated with BW. Associations of preconception trajectories of LTPA with offspring BW may differ by offspring sex and maternal pre-pregnancy overweight-obese status. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring

    OpenAIRE

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D���mello, Anil P

    2016-01-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal prote...

  20. Exposure to Alumina Nanoparticles in Female Mice During Pregnancy Induces Neurodevelopmental Toxicity in the Offspring.

    Science.gov (United States)

    Zhang, Qinli; Ding, Yong; He, Kaihong; Li, Huan; Gao, Fuping; Moehling, Taylor J; Wu, Xiaohong; Duncan, Jeremy; Niu, Qiao

    2018-01-01

    Alumina nanoparticles (AlNP) have been shown to accumulate in organs and penetrate biological barriers which lead to toxic effects in many organ systems. However, it is not known whether AlNP exposure to female mice during pregnancy can affect the development of the central nervous system or induce neurodevelopmental toxicity in the offspring. The present study aims to examine the effect of AlNP on neurodevelopment and associated underlying mechanism. ICR strain adult female mice were randomly divided into four groups, which were treated with normal saline (control), 10 μm particle size of alumina (bulk-Al), and 50 and 13 nm AlNP during entire pregnancy period. Aluminum contents in the hippocampus of newborns were measured and neurodevelopmental behaviors were tracked in the offspring from birth to 1 month of age. Furthermore, oxidative stress and neurotransmitter levels were measured in the cerebral cortex of the adolescents. Our results showed that aluminum contents in the hippocampus of newborns in AlNP-treated groups were significantly higher than those in bulk-Al and controls. Moreover, the offspring delivered by AlNP-treated female mice displayed stunted neurodevelopmental behaviors. Finally, the offspring of AlNP-treated mice demonstrated significantly increased anxiety-like behavior with impaired learning and memory performance at 1 month of age. The underlying mechanism could be related to increased oxidative stress and decreased neurotransmitter levels in the cerebral cortex. We therefore conclude that AlNP exposure of female mice during pregnancy can induce neurodevelopmental toxicity in offspring.

  1. The association between parental bonding and obsessive compulsive disorder in offspring at high familial risk.

    Science.gov (United States)

    Wilcox, Holly C; Grados, Marco; Samuels, Jack; Riddle, Mark A; Bienvenu, Oscar J; Pinto, Anthony; Cullen, Bernadette; Wang, Ying; Shugart, Yin Y; Liang, Kung-Yee; Nestadt, Gerald

    2008-11-01

    The aim of the current study is to estimate the association between parenting factors derived from the Parental Bonding Instrument (PBI) and a lifetime DSM-IV diagnosis of OCD. Data were from approximately 1200 adults from 465 families assessed as part of a large family and genetic study of OCD. The association of three parenting factors, for fathers and mothers, with offspring OCD status were examined; analyses were stratified by parental OCD status and family loading for OCD (multiplex versus sporadic). Three factors were derived by principal components factor analysis of the PBI (maternal and paternal care, overprotection and control). Maternal overprotection was associated with OCD in offspring with familial OCD (familial cases) but only if neither parent was affected with OCD, which suggests independent but additive environmental and genetic risk (OR = 5.9, 95% CI 1.2, 29.9, p = 0.031). Paternal care was a protective factor in those not at high genetic risk (sporadic cases) (OR = 0.2, 95% CI 0.0, 0.8, p = 0.027). Maternal overprotection was also associated with offspring OCD in sporadic families (OR = 2.9, 95% CI 1.3, 6.6, p = 0.012). The finding that parental overprotection and care were not associated with offspring OCD when at least one parent had OCD addressed directly the hypothesis of maternal or paternal OCD adversely impacting parenting. This study provides evidence that aspects of parenting may contribute to the development of OCD among offspring. Prospective studies of children at risk for OCD are needed to explore the direction of causality.

  2. Do children born to teenage parents have lower adult intelligence? A prospective birth cohort study.

    Science.gov (United States)

    Khatun, Mohsina; Al Mamun, Abdullah; Scott, James; William, Gail M; Clavarino, Alexandra; Najman, Jake M

    2017-01-01

    Teenage motherhood has been associated with a wide variety of negative offspring outcomes including poorer cognitive development. In the context of limitations of previous research, this paper assesses the contemporary relevance of this finding. In this study we investigate the long-term cognitive status (IQ) among 21 year adult offspring born to teenage parents using the Mater University Study of Pregnancy- a prospective birth cohort study, which recruited all pregnant mothers attending a large obstetrical hospital in Brisbane, Australia, from 1981 to 1983. The analyses were restricted to a sub-sample of 2643 mother-offspring pair. Offspring IQ was measured using the Peabody Picture Vocabulary Test at 21 year. Parental age was reported at first clinic visit. Offspring born to teenage mothers (parental socioeconomic status, maternal IQ, maternal smoking and binge drinking in pregnancy, birthweight, breastfeeding and parenting style attenuates the association, though the effect remains statistically significant (-1.4 IQ points; 95% CI: -2.8,-0.1). Similarly the risk of offspring having low IQ remained marginally significantly higher in those born to teenage mothers (OR 1.3; 95% CI: 1.0, 1.9). In contrast, teenage fatherhood is not associated with adult offspring IQ, when adjusted for maternal age. Although the reduction in IQ is quantitatively small, it is indicative of neurodevelopmental disadvantage experienced by the young adult offspring of teenage mothers. Our results suggest that public policy initiatives should be targeted not only at delaying childbearing in the population but also at supporting early life condition of children born to teenage mothers to minimize the risk for disadvantageous outcomes of the next generation.

  3. Maternal and offspring intelligence in relation to BMI across childhood and adolescence.

    Science.gov (United States)

    Wraw, Christina; Deary, Ian J; Der, Geoff; Gale, Catharine R

    2018-01-30

    The present study tested the association between both mothers' and offspring's intelligence and offspring's body mass index (BMI) in youth. Participants were members of the National Longitudinal Survey of Youth 1979 (NLSY-79) Children and Young Adults cohort (n = 11,512) and their biological mothers who were members of the NLSY-79 (n = 4932). Offspring's IQ was measured with the Peabody Individual Achievement Test (PIAT). Mothers' IQ was measured with the Armed Forces Qualification Test (AFQT). A series of regression analyses tested the association between IQ and offspring's BMI by age group, while adjusting for pre-pregnancy BMI and family SES. The analyses were stratified by sex and ethnicity (non-Black and non-Hispanic, Black, and Hispanic). The following associations were observed in the fully adjusted analyses. For the non-Blacks and non-Hispanics, a SD increment in mothers' IQ was negatively associated with daughters' BMI across all age-groups, ranging from β = -0.12 (95% CI -0.22 to -0.02, p = 0.021) in late childhood, to β = -0.17 (95% C.I. -0.27 to -0.07, p = 0001), in early adolescence and a SD increment in boys' IQ was positively associated with their BMI in early adolescence β = 0.09 (95% CI 0.01-0.18, p = 0.031). For Blacks, there was a non-linear relationship between mothers' IQ and daughters' BMI across childhood and between girls' IQ and BMI across adolescence. There was a positive association between mothers' IQ and sons' BMI in early adolescence (β = 0.17, 95% CI 0.02-0.32, p = 0.030). For Hispanic boys, there was a positive IQ-BMI association in late childhood (β = 0.19, 95% CI 0.05-0.33, p = 0.008) and early adolescence (β = 0.17, 95% CI 0.04-0.31, p = 0.014). Mothers' IQ and offspring's IQ were associated with offspring's BMI. The relationships varied in direction and strength across ethnicity, age group and sex. Obesity interventions may benefit from acknowledging the heterogeneous

  4. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model.

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    Qi Li

    Full Text Available OBJECTIVES: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. METHOD: We used an established mouse model of maternal immune activation (MIA by the viral mimic PolyI:C administered in early (day 9 or late (day 17 gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. RESULTS: PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4(th ventricle volume but did not disrupt sensorimotor gating. CONCLUSIONS: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.

  5. Sexual Risk Behaviors in the Adolescent Offspring of Parents with Bipolar Disorder: Prospective Associations with Parents' Personality and Externalizing Behavior in Childhood.

    Science.gov (United States)

    Nijjar, Rami; Ellenbogen, Mark A; Hodgins, Sheilagh

    2016-10-01

    We recently reported that adolescent and young adult offspring of parents with bipolar disorder (OBD), relative to control offspring, were more likely to engage in sexual risk behaviors (SRBs). The present prospective study aimed to determine the contribution of parents' personality and offspring behaviour problems in middle childhood to offspring SRBs 10 years later. We hypothesized that offspring externalizing problems in childhood would mediate the relationship between parents' personality traits of neuroticism and agreeableness and adolescent SRBs. Furthermore, we expected these associations to be more robust among the OBD than controls. At baseline, 102 offspring (52 OBD and 50 controls) aged between 4 and 14 years were assessed along with their parents, who completed a self-report personality measure and child behavior rating. Behaviour ratings were also obtained from the children's teachers. Ten years later the offspring completed an interview assessing SRBs. Mediation analyses using bootstrapping revealed that, after controlling for age and presence of an affective disorder, externalizing behaviors served as a pathway through which high parental neuroticism, low parental agreeableness, and low parental extraversion were related to SRBs in offspring. Moderated mediation analyses revealed that the relationship between parental neuroticism and childhood externalizing problems was stronger for OBD than controls. These findings add to our previous results showing parents' personality contributes to intergenerational risk transfer through behavioral problems in middle childhood. These results carry implications for optimal timing of preventative interventions in the OBD.

  6. Childhood IQ of parents related to characteristics of their offspring: linking the Scottish Mental Survey 1932 to the Midspan Family Study

    OpenAIRE

    Hart, C L; Deary, Ian J; Davey Smith, G; Upton, M N; Whalley, Lawrence J; Starr, John M; Hole, D J; Wilson, V; Watt, G C M

    2005-01-01

    The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose,offspring took part in the Midspan Family study in 1996. There were 286 of...

  7. Prenatal Exposure to LPS Alters The Intrarenal RAS in Offspring, Which Is Ameliorated by Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Ding, Xian-Fei; Sun, Mou; Guan, Fang-Xia; Guo, Li-Na; Zhang, Yan-Yan; Wan, You-Dong; Zhang, Xiao-Juan; Yu, Yan-Wu; Ma, Shan-Shan; Yao, Hai-Mu; Yao, Rui; Zhang, Rui-Fang; Sun, Tong-Wen; Kan, Quan-Cheng

    2017-11-06

    Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0.79 mg/kg LPS, respectively, on the 8th, 10th, and 12th days of gestation; an ADSCs group, which was intravenously injected with 1.8 × 107 ADSCs on the 8th, 10th, and 12th days of gestation; and an LPS + ADSCs group, which received a combination of the treatments administered to the LPS and ADSCs groups. Prenatal LPS exposure increased blood pressure, Ang II expression, Ang II-positive, monocyte and lymphocyte, apoptotic cells in the kidney, and induced renal histological changes in offspring; however, the LPS and control groups did not differ significantly with respect to plasma renin activity levels, Ang II levels, or renal function. ADSCs treatment attenuated the blood pressure and also ameliorated the other effects of LPS-treated adult offspring. Prenatal exposure to LPS activates the intrarenal RAS but not the circulating RAS and thus induces increases in blood pressure in adult offspring; however, ADSCs treatment attenuates the blood pressure increases resulting from LPS exposure and also ameliorates the other phenotypic changes induced by LPS treatment by inhibiting intrarenal RAS activation. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Effects of the Use of Assisted Reproduction and High Caloric Diet Consumption on Body Weight and Cardiovascular Health of Juvenile Mouse Offspring

    Science.gov (United States)

    Schenewerk, Angela L.; Ramírez, Francisco; Foote, Christopher; Ji, Tieming; Martínez-Lemus, Luis A.; Rivera, Rocío Melissa

    2013-01-01

    Maternal obesity and the use of assisted reproductive technologies (ART) are two suboptimal developmental environments that can lead to offspring obesity and cardiovascular disease. We hypothesized that these environments independently and synergistically adversely affect the offspring’s weight and cardiovascular performance at ∼7 weeks of age. Mice were fed either 24% fat and 17.5% high fructose corn syrup (HF) or maintenance chow (5% fat; LF). Dams were subdivided into no-ART and ART groups. ART embryos were cultured in Whitten’s medium and transferred into pseudopregnant recipients consuming the same diet as the donor. Offspring were fed the same diet as the mother. Body weights (BW) were measured weekly and mean arterial pressure (MAP) was collected through carotid artery catheterization at sacrifice (55 ± 0.5 days old). Expression of genes involved in cardiovascular remodeling was measured in thoracic aorta using qRT-PCR, and levels of reactive oxygen species were measured intracellularly and extracellularly in mesenteric resistance arteries. ART resulted in increased BW at weaning. This effect decreased over time and diet was the predominant determinant of BW by sacrifice. Males had greater MAP than females (p=0.002) and HF consumption was associated with greater MAP regardless of sex (p<0.05). Gene expression was affected by sex (p<0.05) and diet (p<0.1). Lastly, the use of ART resulted in offspring with increased intracellular ROS (p=0.05). In summary, exposure to an obesogenic diet pre- and/or post-natally affects weight, MAP, and gene expression while ART increases oxidative stress in mesenteric resistance arteries of juvenile offspring, no synergistic effects were observed. PMID:24163396

  9. Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion.

    Directory of Open Access Journals (Sweden)

    Michelle Erin Miller

    Full Text Available Meis1 is recognized as an important transcriptional regulator in hematopoietic development and is strongly implicated in the pathogenesis of leukemia, both as a Hox transcription factor co-factor and independently. Despite the emerging recognition of Meis1's importance in the context of both normal and leukemic hematopoiesis, there is not yet a full understanding of Meis1's functions and the relevant pathways and genes mediating its functions. Recently, several conditional mouse models for Meis1 have been established. These models highlight a critical role for Meis1 in adult mouse hematopoietic stem cells (HSCs and implicate reactive oxygen species (ROS as a mediator of Meis1 function in this compartment. There are, however, several reported differences between these studies in terms of downstream progenitor populations impacted and effectors of function. In this study, we describe further characterization of a conditional knockout model based on mice carrying a loxP-flanked exon 8 of Meis1 which we crossed onto the inducible Cre localization/expression strains, B6;129-Gt(ROSA26Sor(tm1(Cre/ERTNat/J or B6.Cg-Tg(Mx1-Cre1Cgn/J. Findings obtained from these two inducible Meis1 knockout models confirm and extend previous reports of the essential role of Meis1 in adult HSC maintenance and expansion and provide new evidence that highlights key roles of Meis1 in both megakaryopoiesis and erythropoiesis. Gene expression analyses point to a number of candidate genes involved in Meis1's role in hematopoiesis. Our data additionally support recent evidence of a role of Meis1 in ROS regulation.

  10. Parents' Education and their Adult Offspring's Other-Regarding Behavior

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Haagen

    Does socioeconomic background when measured by parental educational attainment explain the heterogeneity in adults' other-regarding preferences? I test this by using data from two online experiments -- a Dictator Game and a Trust Game that were conducted with a broad sample of the Danish adult...... population. I match the experimental data with high-quality data from the Danish population registers about my subjects and their parents. Whereas previous studies have found socioeconomic status, including parental educational attainment, to be predictive for children's generosity, I find no such evidence...... among adults. This result is robust across age groups and genders. I provide two explanations for this. First, sociodemographic characteristics in general appear to be poor predictors of adults' other-regarding behavior. Second, by using Danish survey data, I find that Danish parents' educational...

  11. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

    Science.gov (United States)

    Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

    2017-03-01

    Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

  12. Effect of Cell-Phone Radiation in Pregnancy on Serum Levels of Sexual Hormones and Dynastic Cells in adult Female Offspring in Rats

    Directory of Open Access Journals (Sweden)

    ebrahim Hosseini

    2016-04-01

    Full Text Available Background & objectives: The teratogenic effects of electromagnetic radiation on different processes of growth caused many concerns related to the harmful effects of cell-phone radiation on human health. Therefore, the aim of this study was to investigate the effects of cell-phone radiation on estrogen, progesterone, FSH and LH hormones together with dynastic sexual cells of adult female offspring of pregnant rats affected by these radiations. Methods: In this experimental study, 24 pregnant female rats divided into 3 groups including the control, sham and experimental groups were used. The control group received no radiation and the experimental group was exposed to cell-phone radiation at the beginning of pregnancy (4 hours daily for 14 days. The control group was exposed around turning-on cell-phone without conversation over the same period. After giving birth and after maturity, 10 female offsprings of different groups separated and after phlebotomizing, sexual hormones levels was measured and by separating the ovaries, ovarian follicles species were counted. The results analyzed using ANOVA and T tests. Differences in statistical analysis of data were considered significant at p<0.05. Results: The results showed that the pregnant female exposure to cell-phone radiation caused significant increase in the size and weight of the ovaries and atresic follicles (p<0.05 without significant effect on the number of primary and secondary follicles, antral, graph, primordial, corpus luteum and sexual hormones. Conclusion: Exposure to cell-phone radiations caused increase in the size, weight and atresic follicles of offspring’s ovaries in pregnant females

  13. Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring

    DEFF Research Database (Denmark)

    Vinggaard, Anne; Christiansen, Sofie; Laier, Peter

    2005-01-01

    . Behavioral studies showed that the activity level and sweet preference of adult males were significantly increased. Overall these results strongly indicate that prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal...... of reproductive organs, affecting androgen-regulated gene expressions, and increasing luteinizing hormone (LH) levels. The purpose of this study was to investigate reproductive toxic effects after exposure during gestation and lactation to prochloraz alone and a mixture of five pesticides (deltamethrin...

  14. Dissection of Hippocampal Dentate Gyrus from Adult Mouse

    Science.gov (United States)

    Hagihara, Hideo; Toyama, Keiko; Yamasaki, Nobuyuki; Miyakawa, Tsuyoshi

    2009-01-01

    The hippocampus is one of the most widely studied areas in the brain because of its important functional role in memory processing and learning, its remarkable neuronal cell plasticity, and its involvement in epilepsy, neurodegenerative diseases, and psychiatric disorders. The hippocampus is composed of distinct regions; the dentate gyrus, which comprises mainly granule neurons, and Ammon's horn, which comprises mainly pyramidal neurons, and the two regions are connected by both anatomic and functional circuits. Many different mRNAs and proteins are selectively expressed in the dentate gyrus, and the dentate gyrus is a site of adult neurogenesis; that is, new neurons are continually generated in the adult dentate gyrus. To investigate mRNA and protein expression specific to the dentate gyrus, laser capture microdissection is often used. This method has some limitations, however, such as the need for special apparatuses and complicated handling procedures. In this video-recorded protocol, we demonstrate a dissection technique for removing the dentate gyrus from adult mouse under a stereomicroscope. Dentate gyrus samples prepared using this technique are suitable for any assay, including transcriptomic, proteomic, and cell biology analyses. We confirmed that the dissected tissue is dentate gyrus by conducting real-time PCR of dentate gyrus-specific genes, tryptophan 2,3-dioxygenase (TDO2) and desmoplakin (Dsp), and Ammon's horn enriched genes, Meis-related gene 1b (Mrg1b) and TYRO3 protein tyrosine kinase 3 (Tyro3). The mRNA expressions of TDO2 and Dsp in the dentate gyrus samples were detected at obviously higher levels, whereas Mrg1b and Tyro3 were lower levels, than those in the Ammon's horn samples. To demonstrate the advantage of this method, we performed DNA microarray analysis using samples of whole hippocampus and dentate gyrus. The mRNA expression of TDO2 and Dsp, which are expressed selectively in the dentate gyrus, in the whole hippocampus of alpha

  15. Centenarian offspring: start healthier and stay healthier.

    Science.gov (United States)

    Adams, Emily R; Nolan, Vikki G; Andersen, Stacy L; Perls, Thomas T; Terry, Dellara F

    2008-11-01

    To assess the relative incidence of age-related diseases in a group of centenarian offspring who have thus far been considered to be predisposed to "healthy" aging. Longitudinal study. Nationwide sample. Four hundred forty centenarian offspring and 192 referent cohort subjects who met inclusion criteria of having initial and follow-up health questionnaire data available. Median age of both cohorts was 72 at the initial health questionnaire. Initial health questionnaires were collected from 1997 to 2006. Follow-up questionnaires were collected from 2004 to 2007. The mean period of follow-up was 3.5+/-1.7 years for the centenarian offspring and 3.9+/-2.2 years for the referent cohort. During the follow-up period, centenarian offspring had a 78% lower risk of myocardial infarction (Padvantages over time over similarly aged referent cohort subjects. These findings reinforce the notion that there may be physiological reasons that longevity runs in families and that centenarian offspring are more likely to age in better cardiovascular health and with a lower mortality than their peers.

  16. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring.

    Science.gov (United States)

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-01-01

    Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet) or a low chromium diet (LC, 0.14 mg chromium/kg diet) during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON), while others remained on the same diet (CON-CON, or LC-LC) for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA methylation which

  17. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring.

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    Full Text Available Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet or a low chromium diet (LC, 0.14 mg chromium/kg diet during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON, while others remained on the same diet (CON-CON, or LC-LC for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA

  18. Comparison of iron status and insulin resistance between non-diabetic offspring of type 2 diabetics and non-diabetic offspring of non-diabetics

    International Nuclear Information System (INIS)

    Zafar, U.; Qureshi, H.J.

    2015-01-01

    Insulin resistance is positively correlated with body iron. It is unclear whether iron is a cause or an outcome of insulin resistance. Insulin resistance precedes type 2 diabetes mellitus. Offspring of type 2 diabetics are insulin resistant as compared to those of the non-diabetics. The present study was designed to compare and correlate insulin resistance with iron parameters (including serum ferritin, transferrin saturation and blood haemoglobin) in non-diabetic offspring of type 2 diabetics and non-diabetic offspring of non-diabetics. Methods: It was a cross-sectional study, conducted on one hundred and twenty male subjects 20-40 years of age. They were divided into two groups, each group having 60 subjects. Group A included non-diabetic offspring of type 2 diabetics, while Group B included non-diabetic offspring of non-diabetics. Fasting blood sample was taken and examined for glucose, haemoglobin, insulin, iron, TIBC and ferritin. Data was analysed by SPSS-17. Results: Insulin resistance and iron parameters were significantly higher (p<0.05) in non-diabetic offspring of type 2 diabetics as compared to those of the non-diabetics. There was significant positive correlation (p=0.027) between insulin resistance and serum iron in non-diabetic offspring of type 2 diabetics. There was also significant positive correlation between insulin resistance and serum iron, transferrin saturation and haemoglobin in non-diabetic offspring of non-diabetics. Conclusion: Non-diabetic offspring of type 2 diabetics have iron load and insulin resistance, that predispose them to the development of type 2 diabetes. (author)

  19. Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

    Science.gov (United States)

    Wu, Kay L H; Wu, Chih-Wei; Tain, You-Lin; Huang, Li-Tung; Chao, Yung-Mei; Hung, Chun-Ying; Wu, Jin-Cheng; Chen, Siang-Ru; Tsai, Pei-Chia; Chan, Julie Y H

    2016-04-01

    Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

  1. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

    International Nuclear Information System (INIS)

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-01-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

  2. Birth by cesarean section in relation to adult offspring overweight and biomarkers of cardiometabolic risk

    DEFF Research Database (Denmark)

    Hansen, S; Halldorsson, T I; Olsen, S F

    2018-01-01

    insulin, leptin and adiponectin, and lipid concentrations. RESULTS: In the cohort, 7% were born by C-section, and at age 20 years, 18% of the offspring had a BMI ⩾25 kg m-2. Birth by C-section was associated with increased odds of overweight or obesity at 20 years (Odds ratio=2.17 (95% confidence interval...

  3. Subordinate Males Sire Offspring in Madagascar Fish-eagle (Haliaeetus Vociferoides) Polyandrous Breeding Groups

    OpenAIRE

    Tingay, Ruth E.; Culver, Melanie; Hallerman, Eric M.; Fraser, James D.; Watson, Richard T.

    2002-01-01

    The island endemic Madagascar Fish-Eagle (Haliaeetus vociferoides) is one of the most endangered birds of prey. Certain populations in west-central Madagascar sometimes exhibit a third, and sometimes a fourth, adult involved in breeding activities at a nest. We applied DNA fingerprinting to assess relatedness among 17 individuals at four nests. In all nests with young, a subordinate rather than the dominant male sired the offspring. Within-nest relatedness comparisons showed that some dominan...

  4. Cues of maternal condition influence offspring selfishness.

    Science.gov (United States)

    Wong, Janine W Y; Lucas, Christophe; Kölliker, Mathias

    2014-01-01

    The evolution of parent-offspring communication was mostly studied from the perspective of parents responding to begging signals conveying information about offspring condition. Parents should respond to begging because of the differential fitness returns obtained from their investment in offspring that differ in condition. For analogous reasons, offspring should adjust their behavior to cues/signals of parental condition: parents that differ in condition pay differential costs of care and, hence, should provide different amounts of food. In this study, we experimentally tested in the European earwig (Forficula auricularia) if cues of maternal condition affect offspring behavior in terms of sibling cannibalism. We experimentally manipulated female condition by providing them with different amounts of food, kept nymph condition constant, allowed for nymph exposure to chemical maternal cues over extended time, quantified nymph survival (deaths being due to cannibalism) and extracted and analyzed the females' cuticular hydrocarbons (CHC). Nymph survival was significantly affected by chemical cues of maternal condition, and this effect depended on the timing of breeding. Cues of poor maternal condition enhanced nymph survival in early broods, but reduced nymph survival in late broods, and vice versa for cues of good condition. Furthermore, female condition affected the quantitative composition of their CHC profile which in turn predicted nymph survival patterns. Thus, earwig offspring are sensitive to chemical cues of maternal condition and nymphs from early and late broods show opposite reactions to the same chemical cues. Together with former evidence on maternal sensitivities to condition-dependent nymph chemical cues, our study shows context-dependent reciprocal information exchange about condition between earwig mothers and their offspring, potentially mediated by cuticular hydrocarbons.

  5. Cues of maternal condition influence offspring selfishness.

    Directory of Open Access Journals (Sweden)

    Janine W Y Wong

    Full Text Available The evolution of parent-offspring communication was mostly studied from the perspective of parents responding to begging signals conveying information about offspring condition. Parents should respond to begging because of the differential fitness returns obtained from their investment in offspring that differ in condition. For analogous reasons, offspring should adjust their behavior to cues/signals of parental condition: parents that differ in condition pay differential costs of care and, hence, should provide different amounts of food. In this study, we experimentally tested in the European earwig (Forficula auricularia if cues of maternal condition affect offspring behavior in terms of sibling cannibalism. We experimentally manipulated female condition by providing them with different amounts of food, kept nymph condition constant, allowed for nymph exposure to chemical maternal cues over extended time, quantified nymph survival (deaths being due to cannibalism and extracted and analyzed the females' cuticular hydrocarbons (CHC. Nymph survival was significantly affected by chemical cues of maternal condition, and this effect depended on the timing of breeding. Cues of poor maternal condition enhanced nymph survival in early broods, but reduced nymph survival in late broods, and vice versa for cues of good condition. Furthermore, female condition affected the quantitative composition of their CHC profile which in turn predicted nymph survival patterns. Thus, earwig offspring are sensitive to chemical cues of maternal condition and nymphs from early and late broods show opposite reactions to the same chemical cues. Together with former evidence on maternal sensitivities to condition-dependent nymph chemical cues, our study shows context-dependent reciprocal information exchange about condition between earwig mothers and their offspring, potentially mediated by cuticular hydrocarbons.

  6. Parenting styles and emerging adult drug use in Cebu, the Philippines.

    Science.gov (United States)

    Hock, Rebecca S; Hindin, Michelle J; Bass, Judith K; Surkan, Pamela J; Bradshaw, Catherine P; Mendelson, Tamar

    Parenting style is a potent and malleable influence on emerging adult substance use. Most of the parenting-substance use literature has been conducted in Western populations and it is unknown whether findings are generalizable to other cultures and contexts. We extended the parenting-substance use literature to a cohort of emerging adults in the Philippines using the Cebu Longitudinal Health and Nutrition Survey. We assessed associations between mothers' and fathers' parenting styles (authoritative, permissive, authoritarian, and neglectful) reported by offspring at age 18 and odds of offspring-reported drug use three years later, adjusted for a range of offspring- and parent/household-level characteristics. Females were dropped from analyses due to low prevalence of drug users. We found that many emerging adults in Cebu reported having used drugs, particularly methamphetamine-a dangerous drug with high abuse potential. Authoritative (warm, firm) mothering was significantly associated with sons' reduced odds of drug use and neglectful fathering was related at a trend level with sons' increased odds of having tried drugs. Findings underscore the relation of parenting styles to emerging adults' drug use and add to the literature on cross-cultural variability in parenting styles.

  7. Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring.

    NARCIS (Netherlands)

    Siemelink, M.; Verhoef, A.; Dormans, J.A.M.A.; Span, P.N.; Piersma, A.H.

    2002-01-01

    AIMS/HYPOTHESIS. We investigated of the effects of fatty acid composition of the maternal diet on fetal and postnatal growth, morphology of the pancreas and glucose metabolism and muscle hexosamine concentrations in the adult offspring of rats. METHODS. High-fat diets enriched with either saturated

  8. The Dutch Bipolar Offspring Study: 12-Year Follow-Up

    OpenAIRE

    Mesman, Esther; Nolen, Willem A.; Reichart, Catrien G.; Wals, Marjolein; Hillegers, Manon N. J.

    2013-01-01

    Objective: Offspring of bipolar parents have a genetically increased risk of developing mood disorders. In a longitudinal study, the authors followed a bipolar offspring cohort from adolescence into adulthood to determine the onset, prevalence, and early course of mood disorders and other psychopathology. Method: The Dutch bipolar offspring cohort is a fixed cohort initiated in 1997 (N=140; age range at baseline, 12-21 years). Bipolar offspring were psychiatrically evaluated at baseline and a...

  9. Environmental and parental influences on offspring health and growth in great tits (Parus major.

    Directory of Open Access Journals (Sweden)

    Simon R A Pickett

    Full Text Available Sexual selection requires both that there is heritable variation in traits related to fitness, and that either some of this variation is linked to traits of the parents, and/or that there are direct benefits of choosing particular individuals as mates. This suggests that if direct benefits are important offspring performance should be predicted by traits of the rearing adults. But if indirect benefits are more significant offspring performance should be predicted by traits of the adults at the nest-of-origin. We conducted cross-fostering experiments in great tits (Parus major over four years, in two of which we manipulated environmental conditions by providing supplemental food. In a third year, some nestlings were directly supplemented with carotenoids. Nestlings in broods whose rearing adults received supplemental food were heavier and had improved immune responses even when controlling for body mass. Nestling immune function was related to measures of the yellow plumage color of both the rearing male and the putative father. Nestling body mass was influenced by the coloration of both the rearing female and the genetic mother. Our results suggest that features of both their social and putative genetic parents influence nestling health and growth. From this it would appear that females could be gaining both direct and indirect benefits through mate choice of male plumage traits and that it would be possible for males to similarly gain through mate choice of female traits.

  10. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

    International Nuclear Information System (INIS)

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2008-01-01

    ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD 50 ; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics

  11. Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

    Science.gov (United States)

    Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L

    2015-09-01

    The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.

  12. When to care for, abandon, or eat your offspring: the evolution of parental care and filial cannibalism.

    Science.gov (United States)

    Klug, Hope; Bonsall, Michael B

    2007-12-01

    Parental care and filial cannibalism (the consumption of one's own offspring) co-occur in many animals. While parental care typically increases offspring survival, filial cannibalism involves the killing of one's young. Using an evolutionary ecology approach, we evaluate the importance of a range of factors on the evolution of parental care and filial cannibalism. Parental care, no care/total abandonment, and filial cannibalism evolved and often coexisted over a range of parameter space. While no single benefit was essential for the evolution of filial cannibalism, benefits associated with adult or offspring survival and/or reproduction facilitated the evolution of cannibalism. Our model highlights the plausibility of a range of alternative hypotheses. Specifically, the evolution of filial cannibalism was enhanced if (1) parents could selectively cannibalize lower-quality offspring, (2) filial cannibalism increased egg maturation rate, (3) energetic benefits of eggs existed, or (4) cannibalism increased a parent's reproductive rate (e.g., through mate attractiveness). Density-dependent egg survivorship alone did not favor the evolution of cannibalism. However, when egg survival was density dependent, filial cannibalism invaded more often when the density dependence was relatively more intense. Our results suggest that population-level resource competition potentially plays an important role in the evolution of both parental care and filial cannibalism.

  13. Effects of paternal age and offspring cognitive ability in early adulthood on the risk of schizophrenia and related disorders

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Pedersen, Carsten B; Nordentoft, Merete

    2014-01-01

    Advanced paternal age (APA) and intelligence quotient (IQ) are both associated with the risk of schizophrenia spectrum disorder (SSD) in young adult offspring. We hypothesized that the offspring SSD risk gradient associated with paternal age is mediated by offspring IQ. We investigated joint...... the incidence rate ratio (IRR) of SSD. During the follow-up, 528 men developed SSD (incidence rate [IR] 5.2 and 8.6 per 10,000 person-years in the first and second cohorts, respectively). APA was associated with higher risk of SSD (IRR, 1.32; 95% CI, 1.10-1.60 per a ten-year increase in paternal age). A higher...... IQ was associated with lower SSD risk (IRR, 0.68; 95% confidence interval [CI], 0.63-0.74 per one SD increase). The IR of SSD was higher among persons who were draft-exempt for health reasons (APA-related SSD (individuals...

  14. Vitamin D status during Pregnancy and Aspects of Offspring Health

    Directory of Open Access Journals (Sweden)

    Jane Halliday

    2010-03-01

    Full Text Available Low maternal vitamin D levels during pregnancy have been linked to various health outcomes in the offspring, ranging from periconceptional effects to diseases of adult onset. Maternal and infant cord 25(OHD levels are highly correlated. Here, we review the available evidence for these adverse health effects. Most of the evidence has arisen from observational epidemiological studies, but randomized controlled trials are now underway. The evidence to date supports that women should be monitored and treated for vitamin D deficiency during pregnancy but optimal and upper limit serum 25(OHD levels during pregnancy are not known.

  15. Risks to the offspring from parental occupational exposures

    International Nuclear Information System (INIS)

    Haas, J.F.; Schottenfeld, D.

    1979-01-01

    Risks to the offspring of workers with occupational chemical exposures may derive from mutagenic, teratogenic or carcinogenic effects of industrial agents to which the parents are exposed. Evidence for impaired pregnancies and hazards to the offspring of working populations with chemical exposures is, however, very limited. Evidence is reviewed for hazards to the offspring resulting from parental occupational exposure to vinyl chloride, benzene, chloroprene, radiation and petroleum-derived hydrocarbons. Other environmental and behavioral factors with major effects on pregnancy outcome are considered. These include smoking, alcohol, and drug exposures. An approach to surveillance for chromosomal abnormalities in offspring of occupationally exposed parents is outlined

  16. Maternal omega-3 supplementation increases fat mass in male and female rat offspring

    Directory of Open Access Journals (Sweden)

    Beverly Sara Muhlhausler

    2011-07-01

    Full Text Available Adipogenesis and lipogenesis are highly sensitive to the nutritional environment in utero and in early postnatal life. Omega-3 long chain polyunsaturated fatty acids (LCPUFA inhibit adipogenesis and lipogenesis in adult rats, however it is not known whether supplementing the maternal diet with omega-3 LCPUFA results in reduced fat deposition in the offspring. Female Albino Wistar rats were fed either a standard chow (Control, n=10 or chow designed to provide ~15mg/kg/day of omega-3 LCPUFA, chiefly as docosahexaenoic acid (DHA, throughout pregnancy and lactation (Omega-3, n=11 and all pups were weaned onto a commercial rat chow. Blood and tissues were collected from pups at 3wks and 6wks of age and weights of visceral and subcutaneous fat depots recorded. The expression of adipogenic and lipogenic genes in the subcutaneous and visceral fat depots were determined using qRT-PCR. Birth weight and postnatal growth were not different between groups. At 6 weeks of age, total percentage body fat was significantly increased in both male (5.09 ± 0.32% vs 4.56 ± 0.2%, P<0.04 and female (5.15 ± 0.37% vs 3.89 ± 0.36%, P<0.04 offspring of omega-3 dams compared to controls. The omega-3 LCPUFA content of erythrocyte phospholipids (as a % of total fatty acids was higher in omega-3 offspring (6.7 ± 0.2 % vs 5.6 ± 0.2%, P<0.001. There was no effect of maternal omega-3 LCPUFA supplementation on the expression of adipogenic or lipogenic genes in the offspring in either the visceral or subcutaneous fat depots. We have therefore established that an omega-3 rich environment during pregnancy and lactation in a rodent model increases fat accumulation in both male and female offspring, particularly in subcutaneous depots, but that this effect is not mediated via upregulation adipogenic/lipogenic gene transcription. These data suggest that maternal n-3 LCPUFA supplementation during pregnancy/lactation may not be an effective strategy for reducing fat deposition in

  17. Plant and Animal Reproductive Strategies: Lessons from Offspring Size and Number Tradeoffs

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    K. G. Srikanta Dani

    2017-05-01

    Full Text Available The tradeoff between offspring size and number is ubiquitous and manifestly similar in plants and animals despite fundamental differences between the evolutionary histories of these two major life forms. Fecundity (offspring number primarily affects parental fitness, while offspring size underpins the fitness of parents and offspring. We provide an overview of theoretical models dealing with offspring size and fitness relationships. We follow that with a detailed examination of life-history constraints and environmental effects on offspring size and number, separately in plants and animals. The emphasis is on seed plants, but we endeavor to also summarize information from distinct animal groups—insects, fishes, reptiles, birds, and mammals. Furthermore, we analyse genetic controls on offspring size and number in two model organisms—Arabidopsis and Drosophila. Despite the deep evolutionary divergence between plants and animals, we find four trends in reproductive strategy that are common to both lineages: (i offspring size is generally less variable than offspring number, (ii offspring size increases with increasing parent body size, (iii maternal genes restrict offspring size and increase offspring numbers, while zygotic genes act to increase offspring size; such parent-offspring conflicts are enhanced when there is sibling rivalry, and (iv variation in offspring size increases under sub-optimal (harsh environmental conditions. The most salient difference between plants and animals is that the latter tend to produce larger (fewer offspring under sub-optimal conditions while seed plants invest in smaller (many seeds, suggesting that maternal genetic control over offspring size increases in plants but decreases in animals with parental care. The time is ripe for greater experimental exploration of genetic controls on reproductive allocation and parent-offspring conflicts in plants and animals under sub-optimal (harsh environments.

  18. Impairment of fear memory consolidation in maternally stressed male mouse offspring: evidence for nongenomic glucocorticoid action on the amygdala.

    Science.gov (United States)

    Lee, Eun Jeong; Son, Gi Hoon; Chung, Sooyoung; Lee, Sukwon; Kim, Jeongyeon; Choi, Sukwoo; Kim, Kyungjin

    2011-05-11

    The environment in early life elicits profound effects on fetal brain development that can extend into adulthood. However, the long-lasting impact of maternal stress on emotional learning remains largely unknown. Here, we focus on amygdala-related learning processes in maternally stressed mice. In these mice, fear memory consolidation and certain related signaling cascades were significantly impaired, though innate fear, fear memory acquisition, and synaptic NMDA receptor expression in the amygdala were unaltered. In accordance with these findings, maintenance of long-term potentiation (LTP) at amygdala synapses, but not its induction, was significantly impaired in the maternally stressed animals. Interestingly, amygdala glucocorticoid receptor expression was reduced in the maternally stressed mice, and administration of glucocorticoids (GCs) immediately after fear conditioning and LTP induction restored memory consolidation and LTP maintenance, respectively, suggesting that a weakening of GC signaling was responsible for the observed impairment. Furthermore, microinfusion of a membrane-impermeable form of GC (BSA-conjugated GC) into the amygdala mimicked the restorative effects of GC, indicating that a nongenomic activity of GC mediates the restorative effect. Together, these findings suggest that prenatal stress induces long-term dysregulation of nongenomic GC action in the amygdala of adult offspring, resulting in the impairment of fear memory consolidation. Since modulation of amygdala activity is known to alter the consolidation of emotionally influenced memories allocated in other brain regions, the nongenomic action of GC on the amygdala shown herein may also participate in the amygdala-dependent modulation of memory consolidation.

  19. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    Directory of Open Access Journals (Sweden)

    Fábio da Silva Cunha

    Full Text Available We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib, receiving standard laboratory chow ad libitum; 50% food restricted (FR, receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF, receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels, abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females. Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters, probably through different biological mechanisms.

  20. Production of cloned mice and ES cells from adult somatic cells by nuclear transfer: how to improve cloning efficiency?

    Science.gov (United States)

    Wakayama, Teruhiko

    2007-02-01

    Although it has now been 10 years since the first cloned mammals were generated from somatic cells using nuclear transfer (NT), most cloned embryos usually undergo developmental arrest prior to or soon after implantation, and the success rate for producing live offspring by cloning remains below 5%. The low success rate is believed to be associated with epigenetic errors, including abnormal DNA hypermethylation, but the mechanism of "reprogramming" is unclear. We have been able to develop a stable NT method in the mouse in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. Especially in the mouse, only a few laboratories can make clones from adult somatic cells, and cloned mice are never successfully produced from most mouse strains. However, this technique promises to be an important tool for future research in basic biology. For example, NT can be used to generate embryonic stem (NT-ES) cell lines from a patient's own somatic cells. We have shown that NT-ES cells are equivalent to ES cells derived from fertilized embryos and that they can be generated relatively easily from a variety of mouse genotypes and cell types of both sexes, even though it may be more difficult to generate clones directly. In general, NT-ES cell techniques are expected to be applied to regenerative medicine; however, this technique can also be applied to the preservation of genetic resources of mouse strain instead of embryos, oocytes and spermatozoa. This review describes how to improve cloning efficiency and NT-ES cell establishment and further applications.

  1. Aerobic exercise training performed by parents reduces mice offspring adiposity.

    Science.gov (United States)

    Romero, Paulo Vitor da Silva; Guariglia, Débora Alves; Da Rocha, Francielli Ferreira; Picoli, Caroline de Carvalho; Gilio, Gustavo Renan; Fabricio, Gabriel Sergio; Mathias, Paulo Cesar de Freitas; Moraes, Solange Marta Franzói de; Peres, Sidney Barnabé

    2018-07-01

    The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

  2. Adult plasticity in the subcortical auditory pathway of the maternal mouse.

    Directory of Open Access Journals (Sweden)

    Jason A Miranda

    Full Text Available Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

  3. Adult plasticity in the subcortical auditory pathway of the maternal mouse.

    Science.gov (United States)

    Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

    2014-01-01

    Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

  4. A maternal low protein diet has pronounced effects on mitochondrial gene expression in offspring liver and skeletal muscle; protective effect of taurine

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Olsen, Hanne Lodberg; Frandsen, Lis

    2010-01-01

    Low birth weight is associated with an increased risk of developing impaired glucose tolerance, and eventually type 2 diabetes in adult life. Gestational protein restriction in rodents gives rise to a low birth weight phenotype in the offspring....

  5. Effect of Maternal Administration of Edible Bird’s Nest on the Learning and Memory Abilities of Suckling Offspring in Mice

    Directory of Open Access Journals (Sweden)

    Yong Xie

    2018-01-01

    Full Text Available Although human brains continue developing throughout the underage developmental stages, the infancy period is considered the most important one for the whole life. It has been reported that sialic acid from edible bird’s nest (EBN can facilitate the development of brain and intelligence. In this study, by oral administration of EBN to female mice during the pregnancy or lactation period, the effects of EBN on the levels of sialic acid in mouse milk were determined using high-performance liquid chromatography (HPLC. Furthermore, the spatial learning performances of their offspring were assessed using the Morris water maze test. Additionally, cerebral malondialdehyde (MDA, superoxide dismutase (SOD, choline acetyltransferase (ChAT, and acetylcholinesterase (AChE in cubs nursed by the female mice given the EBN homogenate were examined, while BDNF immunohistochemical staining and neuron count in hippocampi were investigated as well. These results showed that administration with EBN in maternal mice during pregnancy or lactation period can improve the learning and memory functions in their offspring, possibly by increasing the activities of SOD and ChAT and, at the meantime, decreasing the levels of MDA and activities of AChE. Moreover, BDNF levels for CA1, CA2, and CA3 regions in hippocampi and the numbers of dyed neurons in CA1, CA2, CA3, and DG regions among the offspring were significantly enhanced due to the intake of EBN by the maternal mice. We concluded that maternal administration of EBN during the pregnancy and lactation periods can improve the spatial learning performances in the offspring.

  6. Intergenerational determinants of offspring size at birth: a life course and graphical analysis using the Aberdeen Children of the 1950s Study (ACONF).

    Science.gov (United States)

    Morton, Susan M B; De Stavola, Bianca L; Leon, David A

    2014-06-01

    Size at birth has taken on renewed significance due to its now well-established association with many health and health-related outcomes in both the immediate perinatal period and across the entire life course. Optimizing fetal growth to improve both neonatal survival and population health is the focus of much research and policy development, although most efforts have concentrated on either the period of pregnancy itself or the period immediately preceding it. Intergenerational data linked to the Aberdeen Children of the 1950s (ACONF) study were used to examine the influence of grandparental and parental life course biological and social variables on the distribution of offspring size at birth. Guided stepwise multivariable methods and a graphical approach were used to assess the relative importance of these temporally ordered and highly correlated life course measures. Both distal and proximal grandparental and parental life course biological and social factors predicted offspring size at birth. Inequalities in size at birth, according to adult maternal socioeconomic indicators, were found to be largely generated by the continuity of the social environment across generations, and the inequalities in maternal early life growth were predicted by the adult grandparental social environment during the mother's early life. Mother's own size at birth predicted her offspring's intrauterine growth, independent of her adult biological and social characteristics. A mother's childhood social environment and her early growth are both important predictors of her offspring's size at birth. Population strategies aimed at optimizing size at birth require broader social and intergenerational considerations, in addition to focusing on the health of mothers in the immediate pregnancy period. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  7. Family environment and psychopathology in offspring of parents with bipolar disorder.

    Science.gov (United States)

    Lau, Phoebe; Hawes, David J; Hunt, Caroline; Frankland, Andrew; Roberts, Gloria; Wright, Adam; Costa, Daniel S J; Mitchell, Philip B

    2018-01-15

    The aim of this study was to examine the relationship between family environment (cohesion and parental bonding), high-risk status, and psychopathology (internalizing and externalizing problems) among offspring of parents with bipolar disorder (BD), from the perspective of both offspring and their parents. We further tested if family environment mediated the relationship between bipolar risk status and internalizing and externalizing problems. High-risk (n = 90) BD offspring and control (n = 56) offspring aged 12-21 years old, and their parents, completed questionnaires on family cohesion and offspring internalizing and externalizing problems. Offspring also completed a parental bonding questionnaire. Group differences were examined, followed by multi-level mediation analysis with maximum likelihood and robust standard errors. Both offspring and parents in the high-risk group reported higher levels of internalizing and externalizing problems than controls. According to offspring reports, high-risk status, lower maternal and paternal care in parental bonding, was independently associated with internalizing problems. Lower maternal care alone predicted externalizing problems. Family environment did not mediate the relationship between bipolar risk status, and offspring problems. Due to rates of missing data from parent reports of offspring psychopathology, mediation analysis was completed using offspring reports. The offspring-report data presented indicate that low parental warmth and connection were associated with internalizing and externalizing problems as an independent risk factor, in addition to bipolar risk status. The parent-child relationship therefore warrants attention as a potential target for prevention strategies with such families. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Levels of the inflammation marker YKL-40 in young adults exposed to intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Dejgaard, Thomas F; Clausen, Tine D

    2016-01-01

    Plasma levels of the inflammatory marker YKL-40 were investigated in 597 adult offspring born to women with and without diabetes during pregnancy. No association between fetal exposure to maternal hyperglycemia and levels of YKL-40 was found. However, female sex and increasing BMI in the offspring...

  9. Intrauterine and lactation exposure to fluoxetine blunted in the offspring the aortic adaptive response induced by acute restraint stress.

    Science.gov (United States)

    Marques, Bruno V D; Higashi, Carolina M; da S Novi, Daniella R B; Zanluqui, Nagela G; Gregório, Thais F; Pinge-Filho, Phileno; Gerardin, Daniela C C; Pelosi, Gislaine G; Moreira, Estefânia G; Ceravolo, Graziela S

    2017-10-15

    Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants to women during pregnancy. Maternal treatment with fluoxetine can expose fetuses and neonates to higher levels of serotonin that plays a role in stress response. Thus, the aim of the study was to evaluate whether maternal treatment with fluoxetine interferes with aorta reactivity of adult male offspring after acute restraint stress. Wistar rats were gavaged with fluoxetine (5mg/kg/day) or water (control) during pregnancy and lactation. The experiments were performed in adult male offspring, treated or not with reserpine (4mg/Kg, ip, 28h before the experimental protocol). Fluoxetine and control rats were submitted to a single restraint stress session (ST) for 1h. Curves to phenylephrine were performed in thoracic aorta with endothelium. Aortic nitric oxide (NOx) were evaluated by the Griess method. The aortic contraction induced by phenylephrine was similar between control and fluoxetine rats. The acute stress reduced contraction in aorta of control ST compared to control, and L-NAME equaled this response. In fluoxetine rats, ST did not change the aortic constriction. Reserpine treatment restored the vasoconstriction in control ST, but did not interfere with aortic contraction in control, fluoxetine or fluoxetine ST. The NOx concentration was higher in aortas from control ST than control rats, and reserpine reduced NOx levels of control ST. The NOx concentration was similar between fluoxetine and fluoxetine ST rats, treated or not with reserpine. In conclusion, maternal treatment with fluoxetine blunted acute restraint stress-induced NO system activation and aortic adaptation in adult offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. How age affects pointing with mouse and touchpad

    DEFF Research Database (Denmark)

    Hertzum, Morten; Hornbæk, Kasper

    2010-01-01

    pointing with mouse and touchpad. The goal is to provide an integrated analysis of (a) how these three age groups differ in pointing performance, (b) how these differences are affected by the two pointing devices, and (c) how the submovement structure of cursor trajectories may explain performance...... neither more nor less errors than young and adult participants. All three age groups were slower and made more errors with the touchpad than the mouse, but the touchpad slowed down elderly participants more than young participants, who in turn were slowed down more than adult participants. Adult......Effects of age on pointing performance have become increasingly important as computers have become extensively used by still larger parts of the population. This study empirically investigates young (12-14 years), adult (25-33 years), and elderly (61-69 years) participants' performance when...

  11. Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.

    Science.gov (United States)

    Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

    2011-07-01

    Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2016-10-01

    Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha (Gadd45a), aryl hydrocarbon receptor (Ahr), and cyclin-dependent kinase inhibitor 1A (P21) was seen in CSC exposed testes. Apoptotic germ cell death was detected by induction of Fas, FasL, and activated caspase-3. The CSC-exposed males displayed reduction in sperm motility and fertilizing ability and sired pups with reduced body weight and crown-rump length, and smaller litter size with higher numbers of resorption. This model of CSC exposure demonstrates testicular toxicity and developmental defects in the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Does exposure to parental substance use disorders increase offspring risk for a substance use disorder? A longitudinal follow-up study into young adulthood.

    Science.gov (United States)

    Yule, Amy M; Wilens, Timothy E; Martelon, MaryKate; Rosenthal, Lindsay; Biederman, Joseph

    2018-05-01

    The main aim of this study was to examine the risk of exposure to parental substance use disorders (SUD; alcohol or drug abuse or dependence) on the risk for SUD in offspring with and without attention deficit hyperactivity disorder (ADHD) followed into young adult years. Subjects were derived from two longitudinal case-control studies of probands of both sexes, 6-17 years, with and without DSM-III-R ADHD and their parents. Probands were followed for ten years into young adulthood. Probands with a parental history of non-nicotine SUD were included in this analysis. Exposure to SUD was determined by active non-nicotine parental SUD while the parent was living with their child after birth. Cox proportional hazard models were used to calculate the risk of non-nicotine SUD in offspring. 171 of the 404 probands reassessed at ten-year follow up had a family history of parental SUD. 102 probands were exposed to active parental SUD. The average age of our sample was 22.2 ± 3.5 years old. Exposure to maternal but not paternal SUD increased offspring risk for an alcohol use disorder in young adulthood independently of ADHD status (OR: 2.7; 95% CI: 1.1, 6.9; p = 0.04). Exposure to maternal SUD increases the risk for an alcohol use disorder in offspring ten years later in young adult years irrespective of ADHD status. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Persistent sex-by-environment effects on offspring fitness and sex-ratio adjustment in a wild bird population.

    Science.gov (United States)

    Bowers, E Keith; Thompson, Charles F; Sakaluk, Scott K

    2015-03-01

    A major component of sex-allocation theory, the Trivers-Willard model (TWM), posits that sons and daughters are differentially affected by variation in the rearing environment. In many species, the amount of parental care received is expected to have differing effects on the fitness of males and females. When this occurs, the TWM predicts that selection should favour adjustment of the offspring sex ratio in relation to the expected fitness return from offspring. However, evidence for sex-by-environment effects is mixed, and little is known about the adaptive significance of producing either sex. Here, we test whether offspring sex ratios vary according to predictions of the TWM in the house wren (Troglodytes aedon, Vieillot). We also test the assumption of a sex-by-environment effect on offspring using two experiments, one in which we manipulated age differences among nestlings within broods, and another in which we held nestling age constant but manipulated brood size. As predicted, females with high investment ability overproduced sons relative to those with lower ability. Males were also overproduced early within breeding seasons. In our experiments, the body mass of sons was more strongly affected by the sibling-competitive environment and resource availability than that of daughters: males grew heavier than females when reared in good conditions but were lighter than females when in poor conditions. Parents rearing broods with 1:1 sex ratios were more productive than parents rearing broods biased more strongly towards sons or daughters, suggesting that selection favours the production of mixed-sex broods. However, differences in the condition of offspring as neonates persisted to adulthood, and their reproductive success as adults varied with the body mass of sons, but not daughters, prior to independence from parental care. Thus, selection should favour slight but predictable variations in the sex ratio in relation to the quality of offspring that parents are

  15. Adherence to the Mediterranean diet during pregnancy and offspring adiposity and cardiometabolic traits in childhood.

    Science.gov (United States)

    Chatzi, L; Rifas-Shiman, S L; Georgiou, V; Joung, K E; Koinaki, S; Chalkiadaki, G; Margioris, A; Sarri, K; Vassilaki, M; Vafeiadi, M; Kogevinas, M; Mantzoros, C; Gillman, M W; Oken, E

    2017-08-01

    In adults, adherence to the Mediterranean diet has been inversely associated with cardiovascular risk, but the extent to which diet in pregnancy is associated with offspring adiposity is unclear. We aimed to investigate the association between adherence to Mediterranean diet in pregnancy and offspring cardiometabolic traits in two pregnancy cohorts. We studied 997 mother-child pairs from Project Viva in Massachusetts, USA, and 569 pairs from the Rhea study in Crete, Greece. We estimated adherence to the Mediterranean diet with an a priori defined score (MDS) of nine foods and nutrients (0 to 9). We measured child weight, height, waist circumference, skin-fold thicknesses, blood pressure, and blood levels of lipids, c-reactive protein and adipokines in mid-childhood (median 7.7 years) in Viva, and in early childhood (median 4.2 years) in Rhea. We calculated cohort-specific effects and pooled effects estimates with random-effects models for cohort and child age. In Project Viva, the mean (SD, standard deviation) MDS was 2.7 (1.6); in Rhea it was 3.8 (1.7). In the pooled analysis, for each 3-point increment in the MDS, offspring BMI z-score was lower by 0.14 units (95% CI, -0.15 to -0.13), waist circumference by 0.39 cm (95% CI, -0.64 to -0.14), and the sum of skin-fold thicknesses by 0.63 mm (95% CI, -0.98 to -0.28). We also observed lower offspring systolic (-1.03 mmHg; 95% CI, -1.65 to -0.42) and diastolic blood pressure (-0.57 mmHg; 95% CI, -0.98 to -0.16). Greater adherence to Mediterranean diet during pregnancy may protect against excess offspring cardiometabolic risk. © 2017 World Obesity Federation.

  16. A specific immune tolerance toward offspring cells is to exist after the mother lymphocyte infusion.

    Science.gov (United States)

    Xing, Haizhou; Liu, Shiqin; Chen, Xue; Fang, Fang; Wu, Xueqiang; Zhu, Ping

    2017-04-01

    To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10 7 of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected. CFSE+, CFSE-, CD3+, CD8+, CD4+, CD19+, NK1.1+, CD25+, and CD127+ lymphocytes in those samples were analyzed by flow cytometry. The distribution of donor T cells, B cells, NK cells, helper T cells, cytotoxic T cells, and recipient regulatory T cells in the tissues were then analyzed. Maternal lymphocytes were more likely to survive in offspring. At 120h after infusion, the percentages of maternal cells in the offspring were 0.52±0.11% in lymph nodes, 0.97±0.04% in peripheral blood, and 0.97±0.11% in the spleen. Few donor cells, if any, were detected in these tissues at 120h after aunt to child, father to child, and unrelated allogeneic infusions were performed. The subtype proportion of donor lymphocytes changed significantly in the recipient tissues. Recipient Treg cells increased in the mother to child group, but not in the aunt to child, father to child, and unrelated allogeneic groups, suggesting a decreased cellular immune response to allogeneic cells in the mother to child group. At 120h after the infusion, no donor cells were detected in the recipient livers and thymuses of all groups, implying that donor cells were barely able to colonize in the liver and thymus. Specific immune tolerance to maternal lymphocytes exists in offspring. An infusion of maternal donor lymphocytes may produce a relatively persistent effect of adoptive immunotherapy with reduced side-effects. Copyright © 2017 Elsevier GmbH. All rights

  17. Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function.

    Science.gov (United States)

    Thorsell, Annika; Nätt, Daniel

    2016-08-01

    It has been shown that maternal stress and malnutrition, or experience of other adverse events, during the perinatal period may alter susceptibility in the adult offspring in a time-of-exposure dependent manner. The mechanism underlying this may be epigenetic in nature. Here, we summarize some recent findings on the effects on gene-regulation following maternal malnutrition, focusing on epigenetic regulation of peptidergic activity. Numerous neuropeptides within the central nervous system are crucial components in regulation of homeostatic energy-balance, as well as affective health (i.e. health events related to affective disorders, psychiatric disorders also referred to as mood disorders). It is becoming evident that expression, and function, of these neuropeptides can be regulated via epigenetic mechanisms during fetal development, thereby contributing to the development of the adult phenotype and, possibly, modulating disease susceptibility. Here, we focus on two such neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH), both involved in regulation of endocrine function, energy homeostasis, as well as affective health. While a number of published studies indicate the involvement of epigenetic mechanisms in CRH-dependent regulation of the offspring adult phenotype, NPY has been much less studied in this context and needs further work.

  18. Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring

    OpenAIRE

    Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

    2012-01-01

    Background: Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. Objectives and Methods: This study tested the hypothesis that CPEE increases whole-body adiposity and disrup...

  19. Parental psychiatric hospitalisation and offspring schizophrenia

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2009-01-01

    The risk of schizophrenia has been linked with a family history of schizophrenia and less strongly with other psychiatric disorders in family members. Using data from the Copenhagen Perinatal Cohort and from the Danish Psychiatric Case Register, we studied the relationship between offspring risk...... of schizophrenia and a range of psychotic and non-psychotic psychiatric diagnoses in parents. Psychiatric admission data after 1969 were available for 7047 cohort members born between 1959 and 1961, and for 7006 mothers and 6993 fathers. Univariate analysis showed that neurosis, alcohol and substance dependence...... in both parents were associated with elevated risk of offspring schizophrenia; in addition, maternal schizophrenia, affective disorder and personality disorder were associated with elevated risk. Controlling for parental age, parental social status, and parental psychiatric co-diagnosis, offspring risk...

  20. Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children

    Science.gov (United States)

    Sharp, Gemma C; Lawlor, Debbie A; Richmond, Rebecca C; Fraser, Abigail; Simpkin, Andrew; Suderman, Matthew; Shihab, Hashem A; Lyttleton, Oliver; McArdle, Wendy; Ring, Susan M; Gaunt, Tom R; Davey Smith, George; Relton, Caroline L

    2015-01-01

    Background: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. Methods: We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants. Results: Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than associations of paternal obesity, supporting an intrauterine mechanism. There were no consistent associations of gestational weight gain with offspring DNA methylation. In general, sites that were hypermethylated in association with maternal obesity or hypomethylated in association with maternal underweight tended to be positively associated with offspring adiposity, and sites hypomethylated in association with maternal obesity or hypermethylated in association with maternal underweight tended to be inversely associated with offspring adiposity. Conclusions: Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect. We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation. PMID:25855720

  1. Too risky to settle: avian community structure changes in response to perceived predation risk on adults and offspring

    Science.gov (United States)

    Hua, Fangyuan; Fletcher, Robert J.; Sieving, Kathryn E.; Dorazio, Robert M.

    2013-01-01

    Predation risk is widely hypothesized as an important force structuring communities, but this potential force is rarely tested experimentally, particularly in terrestrial vertebrate communities. How animals respond to predation risk is generally considered predictable from species life-history and natural-history traits, but rigorous tests of these predictions remain scarce. We report on a large-scale playback experiment with a forest bird community that addresses two questions: (i) does perceived predation risk shape the richness and composition of a breeding bird community? And (ii) can species life-history and natural-history traits predict prey community responses to different types of predation risk? On 9 ha plots, we manipulated cues of three avian predators that preferentially prey on either adult birds or offspring, or both, throughout the breeding season. We found that increased perception of predation risk led to generally negative responses in the abundance, occurrence and/or detection probability of most prey species, which in turn reduced the species richness and shifted the composition of the breeding bird community. Species-level responses were largely predicted from the key natural-history trait of body size, but we did not find support for the life-history theory prediction of the relationship between species' slow/fast life-history strategy and their response to predation risk.

  2. Maternal or paternal suicide and offspring's psychiatric and suicide-attempt hospitalization risk.

    Science.gov (United States)

    Kuramoto, S Janet; Stuart, Elizabeth A; Runeson, Bo; Lichtenstein, Paul; Långström, Niklas; Wilcox, Holly C

    2010-11-01

    We examined whether the risk for psychiatric morbidity requiring inpatient care was higher for offspring who experienced parental suicide, compared with offspring of fatal accident decedents, and whether the association varied according to the deceased parent's gender. Children and adolescents (0-17 years of age) who experienced maternal (N = 5600) or paternal (N = 17,847) suicide in 1973-2003 in Sweden were identified by using national, longitudinal, population-based registries. Cox regression modeling was used to compare psychiatric hospitalization risks among offspring of suicide decedents and propensity score-matched offspring of accident decedents. Offspring of maternal suicide decedents had increased risk of suicide-attempt hospitalization, after controlling for psychiatric hospitalization for decedents and surviving parents, compared with offspring of maternal accidental decedents. Offspring of paternal suicide decedents had similar risk of suicide-attempt hospitalization, compared with offspring of accident decedents, but had increased risk of hospitalization attributable to depressive and anxiety disorders. The magnitude of risks for offspring suicide-attempt hospitalization was greater for those who experienced maternal versus paternal suicide, compared with their respective control offspring (interaction P = .05; offspring of maternal decedents, adjusted hazard ratio: 1.80 [95% confidence interval: 1.19-2.74]; offspring of paternal decedents, adjusted hazard ratio: 1.14 [95% confidence interval: 0.96-1.35]). Maternal suicide is associated with increased risk of suicide-attempt hospitalization for offspring, beyond the risk associated with maternal accidental death. However, paternal suicide is not associated with suicide-attempt hospitalization. Future studies should examine factors that might differ between offspring who experience maternal versus paternal suicide, including genetic or early environmental determinants.

  3. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

    Science.gov (United States)

    Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

    2015-10-01

    Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Transmission of cultural values among Mexican-origin parents and their adolescent and emerging adult offspring.

    Science.gov (United States)

    Perez-Brena, Norma J; Updegraff, Kimberly A; Umaña-Taylor, Adriana J

    2015-06-01

    The integration of the U.S. and Mexican culture is an important process associated with Mexican-origin youths' adjustment and family dynamics. The current study examined the reciprocal associations in parents' and two offspring's cultural values (i.e., familism and respect) in 246 Mexican-origin families. Overall, mothers' values were associated with increases in youths' values 5 years later. In contrast, youths' familism values were associated with increases in fathers' familism values 5 years later. In addition, developmental differences emerged where parent-to-offspring effects were more consistent for youth transitioning from early to late adolescence than for youth transitioning from middle adolescence to emerging adulthood. Finally, moderation by immigrant status revealed a youth-to-parent effect for mother-youth immigrant dyads, but not for dyads where youth were U.S.-raised. Our findings highlight the reciprocal nature of parent-youth value socialization and provide a nuanced understanding of these processes through the consideration of familism and respect values. As Mexican-origin youth represent a large and rapidly growing segment of the U.S. population, research that advances our understanding of how these youth develop values that foster family cohesion and support is crucial. © 2014 Family Process Institute.

  5. Do children born to teenage parents have lower adult intelligence? A prospective birth cohort study.

    Directory of Open Access Journals (Sweden)

    Mohsina Khatun

    Full Text Available Teenage motherhood has been associated with a wide variety of negative offspring outcomes including poorer cognitive development. In the context of limitations of previous research, this paper assesses the contemporary relevance of this finding. In this study we investigate the long-term cognitive status (IQ among 21 year adult offspring born to teenage parents using the Mater University Study of Pregnancy- a prospective birth cohort study, which recruited all pregnant mothers attending a large obstetrical hospital in Brisbane, Australia, from 1981 to 1983. The analyses were restricted to a sub-sample of 2643 mother-offspring pair. Offspring IQ was measured using the Peabody Picture Vocabulary Test at 21 year. Parental age was reported at first clinic visit. Offspring born to teenage mothers (<20 years have -3.0 (95% Confidence Interval (CI: -4.3, -1.8 points lower IQ compared to children born to mothers ≥20 years and were more likely to have a low IQ (Odds Ratio (OR 1.7; 95% CI: 1.3, 2.3. Adjustment for a range of confounding and mediating factors including parental socioeconomic status, maternal IQ, maternal smoking and binge drinking in pregnancy, birthweight, breastfeeding and parenting style attenuates the association, though the effect remains statistically significant (-1.4 IQ points; 95% CI: -2.8,-0.1. Similarly the risk of offspring having low IQ remained marginally significantly higher in those born to teenage mothers (OR 1.3; 95% CI: 1.0, 1.9. In contrast, teenage fatherhood is not associated with adult offspring IQ, when adjusted for maternal age. Although the reduction in IQ is quantitatively small, it is indicative of neurodevelopmental disadvantage experienced by the young adult offspring of teenage mothers. Our results suggest that public policy initiatives should be targeted not only at delaying childbearing in the population but also at supporting early life condition of children born to teenage mothers to minimize the risk

  6. Teenage parents and their offspring.

    Science.gov (United States)

    Kaufman, J

    1996-06-18

    Teenage parents are cast into adult roles before the role experimentation and identity development tasks of middle adolescence can be completed. Understanding the etiology of this social problem requires an ecological perspective encompassing individual characteristics, person-context variables, and societal factors such as race and social class. Risk factors identified in the literature on adolescent pregnancy in the US include: absence of a future orientation or aspirations, lack of assertiveness and interpersonal skills to control physical intimacy, low socioeconomic status and minority group membership, growing up in a single-parent family, a history of sexual abuse, five or more siblings, a sister or friend who became a teenage mother, lax parental supervision of dating and free time, low self-esteem, and dropping out or failing in school. The limited data on adolescent fathers suggest they have histories of substance use, delinquency, failure to graduate from high school, financial difficulty, and exposure to family violence. The offspring of adolescent parents show a higher incidence of developmental delays and mild mental retardation than children of adults and are at increased risk of child abuse and neglect. Teen parents raised in dysfunctional families tend to perpetuate destructive methods of child rearing and have unrealistic, age-inappropriate expectations for infants and toddlers. Teenage parents' lack of competence can be mitigated, however, by positive living arrangements, a supportive family of origin, peer support groups, quality child care, school-based services, and accurate information about parenting and child development.

  7. Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

    Science.gov (United States)

    Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V

    2016-01-01

    There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.

  8. Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer

    Science.gov (United States)

    Yamazaki, Yukiko; Makino, Hatsune; Hamaguchi-Hamada, Kayoko; Hamada, Shun; Sugino, Hidehiko; Kawase, Eihachiro; Miyata, Takaki; Ogawa, Masaharu; Yanagimachi, Ryuzo; Yagi, Takeshi

    2001-01-01

    When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5–17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells. PMID:11698647

  9. Chronic Prenatal Hypoxia Down-Regulated BK Channel Β1 Subunits in Mesenteric Artery Smooth Muscle Cells of the Offspring

    Directory of Open Access Journals (Sweden)

    Bailin Liu

    2018-02-01

    Full Text Available Background/Aims: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK channels in offspring mesenteric arteries following prenatal hypoxia. Methods: Pregnant rats were exposed to normoxic control (21% O2, Con or hypoxic (10.5% O2, Hy conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR. Results: Prenatal hypoxia increased pressor responses and vasoconstrictions to phenylephrine in the offspring. Whole-cell currents density of BK channels and amplitude of spontaneous transient outward currents (STOCs, not the frequency, were significantly reduced in Hy vascular myocytes. The sensitivity of BK channels to voltage, Ca2+, and tamoxifen were reduced in Hy myocytes, whereas the number of channels per patch and the single-channel conductance were unchanged. Prenatal hypoxia impaired NS1102- and tamoxifen-mediated relaxation in mesenteric arteries precontracted with phenylephrine in the presence of Nω-nitro-L-arginine methyl ester. The mRNA and protein expression of BK channel β1, not the α-subunit, was decreased in Hy mesenteric arteries. Conclusions: Impaired BK channel β1-subunits in vascular smooth muscle cells contributed to vascular dysfunction in the offspring exposed to prenatal hypoxia.

  10. [Psychopathological Profiles of Offspring of Subjects with Bipolar Disorder].

    Science.gov (United States)

    Villa, Esteban Uribe; Briceño, Paola Gutiérrez; Palacio, Juan David; García, Jenny

    2012-03-01

    Bipolar Disorder (BD) has a high heritability and is more prevalent in first-degree relatives with family history. This makes the bipolar offspring (BO) an ideal study group to evaluate the natural history and the prodromal symptoms of this disorder. The main psychopathological findings for this group in various studies are described in this review. Articles comparing the psychopathology of bipolar offspring to either the offspring of other psychiatric patients or the offspring of healthy controls were reviewed. The reviewed studies showed that the BO group had higher rates of affective disorders when compared to the offspring of other psychiatric patients or the offspring of healthy controls. The high prevalence of anxiety disorders, ADHD, and disruptive behavior disorders in this population suggest that such disorders could be considered prodromes of mood disorders. The group of BO had a significantly higher risk of developing a wide range of psychiatric disorders besides BD. More longitudinal studies are needed to characterize this population at risk for BD and to elucidate the risk factors in the progression of this disorder. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  11. The effects of feeding rats diets deficient in folic acid and related methyl donors on the blood pressure and glucose tolerance of the offspring.

    Science.gov (United States)

    Maloney, Christopher A; Hay, Susan M; Rees, William D

    2009-05-01

    In humans poor maternal folate status is associated with a decrease in infant birth weight. As low birth weight increases the risk of cardiovascular and metabolic disease in adults, an inadequate supply of folic acid in the mother's diet may increase the susceptibility of the offspring to disease. We have fed laboratory rats diets deficient in folic acid and the related methyl donors methionine and choline to examine the effects on growth, blood pressure and insulin action in the offspring. Poor folate status transiently increased fetal growth but did not produce a long-term change in body weight. There were, however, small changes in the hearts of the female offspring. When folate deficiency was combined with low intakes of methionine and choline, the kidneys of the male offspring were proportionately smaller, probably because of the limited availability of methionine. There was no effect on the blood pressure of either the male or female offspring. The pancreatic insulin content of fetuses from animals fed the folate-deficient diets were higher than those of the controls. Following an oral glucose challenge, there was a weak trend for glucose-stimulated insulin release to be increased in the offspring of dams fed the folate-deficient diet. The changes in insulin concentrations were, however, much smaller than the corresponding changes observed in the offspring of animals fed protein-deficient diets. These results suggest that folate deficiency during gestation causes modest changes to the insulin axis of the fetus.

  12. Maternal obesity-impaired insulin signaling in sheep and induced lipid accumulation and fibrosis in skeletal muscle of offspring.

    Science.gov (United States)

    Yan, Xu; Huang, Yan; Zhao, Jun-Xing; Long, Nathan M; Uthlaut, Adam B; Zhu, Mei-Jun; Ford, Stephen P; Nathanielsz, Peter W; Du, Min

    2011-07-01

    The prevalence of maternal obesity is increasing rapidly in recent decades. We previously showed that maternal obesity affected skeletal muscle development during the fetal stage. The objective of this study was to evaluate the effects of maternal obesity on the skeletal muscle properties of offspring. Ewes were fed a control diet (100% energy requirement, Con) or an obesogenic diet (150% energy requirement, OB) from 2 mo before pregnancy to weaning. After weaning, the offspring lambs were fed a maintenance diet until 19 mo of age and then ad libitum for 12 wk to measure feed intake. At 22 mo old, the longissimus dorsi (LD) muscle was biopsied. The downstream insulin signaling was lower in OB than Con lambs as shown by reduction in the phosphorylation of protein kinase B, mammalian target of rapamycin, and 4-E binding protein 1. On the other hand, the phosphorylation of protein kinase C and insulin receptor substrate 1 was higher in OB compared to Con lambs. More intramuscular adipocytes were observed in OB compared to Con offspring muscle, and the expression of peroxisome proliferator-activated receptor gamma, an adipocyte marker, was also higher, which was consistent with the higher intramuscular triglyceride content. Both fatty acid transport protein 1 and cluster of differentiation 36 (also known as fatty acid translocase) were increased in the OB group. In addition, higher collagen content was also detected in OB compared to Con offspring. In conclusion, our data show that offspring from obese mothers had impaired insulin signaling in muscle compared with control lambs, which correlates with increased intramuscular triglycerides and higher expression of fatty acid transporters. These data clearly show that maternal obesity impairs the function of the skeletal muscle of offspring, supporting the fetal programming of adult metabolic diseases.

  13. Renal Development and Blood Pressure in Offspring from Dams Submitted to High-Sodium Intake during Pregnancy and Lactation

    Directory of Open Access Journals (Sweden)

    Terezila M. Coimbra

    2012-01-01

    Full Text Available Exposure to an adverse environment in utero appears to programme physiology and metabolism permanently, with long-term consequences for health of the fetus or offspring. It was observed that the offspring from dams submitted to high-sodium intake during pregnancy present disturbances in renal development and in blood pressure. These alterations were associated with lower plasma levels of angiotensin II (AII and changes in renal AII receptor I (AT1 and mitogen-activated protein kinase (MAPK expressions during post natal kidney development. Clinical and experimental evidence show that the renin-angiotensin system (RAS participates in renal development. Many effects of AII are mediated through MAPK pathways. Extracellular signal-regulated protein kinases (ERKs play a pivotal role in cellular proliferation and differentiation. In conclusion, high-sodium intake during pregnancy and lactation can provoke disturbances in renal development in offspring leading to functional and structural alterations that persist in adult life. These changes can be related at least in part with the decrease in RAS activity considering that this system has an important role in renal development.

  14. Rhythmic ganglion cell activity in bleached and blind adult mouse retinas.

    Science.gov (United States)

    Menzler, Jacob; Channappa, Lakshmi; Zeck, Guenther

    2014-01-01

    In retinitis pigmentosa--a degenerative disease which often leads to incurable blindness--the loss of photoreceptors deprives the retina from a continuous excitatory input, the so-called dark current. In rodent models of this disease this deprivation leads to oscillatory electrical activity in the remaining circuitry, which is reflected in the rhythmic spiking of retinal ganglion cells (RGCs). It remained unclear, however, if the rhythmic RGC activity is attributed to circuit alterations occurring during photoreceptor degeneration or if rhythmic activity is an intrinsic property of healthy retinal circuitry which is masked by the photoreceptor's dark current. Here we tested these hypotheses by inducing and analysing oscillatory activity in adult healthy (C57/Bl6) and blind mouse retinas (rd10 and rd1). Rhythmic RGC activity in healthy retinas was detected upon partial photoreceptor bleaching using an extracellular high-density multi-transistor-array. The mean fundamental spiking frequency in bleached retinas was 4.3 Hz; close to the RGC rhythm detected in blind rd10 mouse retinas (6.5 Hz). Crosscorrelation analysis of neighbouring wild-type and rd10 RGCs (separation distance rhythmic RGC spiking in these retinas is driven by a network of presynaptic neurons. The inhibition of glutamatergic ganglion cell input or the inhibition of gap junctional coupling abolished the rhythmic pattern. In rd10 and rd1 retinas the presynaptic network leads to local field potentials, whereas in bleached retinas additional pharmacological disinhibition is required to achieve detectable field potentials. Our results demonstrate that photoreceptor bleaching unmasks oscillatory activity in healthy retinas which shares many features with the functional phenotype detected in rd10 retinas. The quantitative physiological differences advance the understanding of the degeneration process and may guide future rescue strategies.

  15. A theoretical model of the evolution of maternal effects under parent-offspring conflict

    NARCIS (Netherlands)

    Uller, Tobias; Pen, Ido

    The evolution of maternal effects on offspring phenotype should depend on the extent of parent-offspring conflict and costs and constraints associated with maternal and offspring strategies. Here, we develop a model of maternal effects on offspring dispersal phenotype under parent-offspring conflict

  16. Cell proliferation, movement and differentiation during maintenance of the adult mouse adrenal cortex.

    Directory of Open Access Journals (Sweden)

    Su-Ping Chang

    Full Text Available Appropriate maintenance and regeneration of adult endocrine organs is important in both normal physiology and disease. We investigated cell proliferation, movement and differentiation in the adult mouse adrenal cortex, using different 5-bromo-2'-deoxyuridine (BrdU labelling regimens and immunostaining for phenotypic steroidogenic cell markers. Pulse-labelling showed that cell division was largely confined to the outer cortex, with most cells moving inwards towards the medulla at around 13-20 µm per day, though a distinct labelled cell population remained in the outer 10% of the cortex. Pulse-chase-labelling coupled with phenotypic immunostaining showed that, unlike cells in the inner cortex, most BrdU-positive outer cortical cells did not express steroidogenic markers, while co-staining for BrdU and Ki67 revealed that some outer cortical BrdU-positive cells were induced to proliferate following acute adrenocorticotropic hormone (ACTH treatment. Extended pulse-chase-labelling identified cells in the outer cortex which retained BrdU label for up to 18-23 weeks. Together, these observations are consistent with the location of both slow-cycling stem/progenitor and transiently amplifying cell populations in the outer cortex. Understanding the relationships between these distinct adrenocortical cell populations will be crucial to clarify mechanisms underpinning adrenocortical maintenance and long-term adaptation to pathophysiological states.

  17. Offspring of parents who were separated and not speaking to one another have reduced resistance to the common cold as adults.

    Science.gov (United States)

    Murphy, Michael L M; Cohen, Sheldon; Janicki-Deverts, Denise; Doyle, William J

    2017-06-20

    Exposure to parental separation or divorce during childhood has been associated with an increased risk for physical morbidity during adulthood. Here we tested the hypothesis that this association is primarily attributable to separated parents who do not communicate with each other. We also examined whether early exposure to separated parents in conflict is associated with greater viral-induced inflammatory response in adulthood and in turn with increased susceptibility to viral-induced upper respiratory disease. After assessment of their parents' relationship during their childhood, 201 healthy volunteers, age 18-55 y, were quarantined, experimentally exposed to a virus that causes a common cold, and monitored for 5 d for the development of a respiratory illness. Monitoring included daily assessments of viral-specific infection, objective markers of illness, and local production of proinflammatory cytokines. Adults whose parents lived apart and never spoke during their childhood were more than three times as likely to develop a cold when exposed to the upper respiratory virus than adults from intact families. Conversely, individuals whose parents were separated but communicated with each other showed no increase in risk compared with those from intact families. These differences persisted in analyses adjusted for potentially confounding variables (demographics, current socioeconomic status, body mass index, season, baseline immunity to the challenge virus, affectivity, and childhood socioeconomic status). Mediation analyses were consistent with the hypothesis that greater susceptibility to respiratory infectious illness among the offspring of noncommunicating parents was attributable to a greater local proinflammatory response to infection.

  18. In-utero exposure to bereavement and offspring IQ: a Danish national cohort study.

    Directory of Open Access Journals (Sweden)

    Jasveer Virk

    Full Text Available BACKGROUND: Intelligence is a life-long trait that has strong influences on lifestyle, adult morbidity and life expectancy. Hence, lower cognitive abilities are therefore of public health interest. Our primary aim was to examine if prenatal bereavement measured as exposure to death of a close family member is associated with the intelligence quotient (IQ scores at 18-years of age of adult Danish males completing a military cognitive screening examination. METHODS: We extracted records for the Danish military screening test and found kinship links with biological parents, siblings, and maternal grandparents using the Danish Civil Registration System (N = 167,900. The prenatal exposure period was defined as 12 months before conception until birth of the child. We categorized children as exposed in utero to severe stress (bereavement during prenatal life if their mothers lost an elder child, husband, parent or sibling during the prenatal period; the remaining children were included in the unexposed cohort. Mean score estimates were adjusted for maternal and paternal age at birth, residence, income, maternal education, gestational age at birth and birth weight. RESULTS: When exposure was due to death of a father the offsprings' mean IQ scores were lower among men completing the military recruitment exam compared to their unexposed counterparts, adjusted difference of 6.5 standard IQ points (p-value = 0.01. We did not observe a clinically significant association between exposure to prenatal maternal bereavement caused by death of a sibling, maternal uncle/aunt or maternal grandparent even after stratifying deaths only due to traumatic events. CONCLUSION: We found maternal bereavement to be adversely associated with IQ in male offspring, which could be related to prenatal stress exposure though more likely is due to changes in family conditions after death of the father. This finding supports other literature on maternal adversity during fetal

  19. Developmental Exposure to Mild Variable Stress: Adult Offspring Performance in Trace Fear Conditioning after Prenatal and Postnatal Stress

    Science.gov (United States)

    In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress parad...

  20. Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice.

    Science.gov (United States)

    Masuyama, Hisashi; Hiramatsu, Yuji

    2012-07-15

    The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

  1. “What are my chances of developing COPD if one of my parents has the disease?” A systematic review and meta-analysis of prevalence of co-occurrence of COPD diagnosis in parents and offspring

    Science.gov (United States)

    Li, Lok Sze Katrina; Paquet, Catherine; Johnston, Kylie; Williams, Marie T

    2017-01-01

    Introduction Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to life course factors. Consequently, adult offspring of parents with COPD may be at a greater risk of developing COPD. The aim of this study was to review the prevalence of co-occurrence of COPD in adult offspring with one or both parents having COPD independent of specific genetic variations. Methods In total, five databases were searched for original studies in which prevalence of COPD was reported in both offspring (children) and one or both parents. Studies were excluded if COPD was not clearly defined, COPD was linked to specific genetic variations, COPD was combined with other chronic respiratory conditions, or estimates included other first-degree relatives. Data extraction (ie, sample characteristics, prevalence of COPD, and odds ratio [OR] if reported) was completed by two independent reviewers. A meta-analysis of prevalence and OR was conducted, where possible. Results Of the 3,382 citations, 129 full texts were reviewed to include eight studies (six case–control, one cross-sectional, and one cohort) reflecting either prevalence of COPD in offspring of parents with COPD (descendent approach, n=3), which ranged from 0% to 17.3%, or prevalence of people with COPD reporting positive parental history of COPD (antecedent approach, n=5), for which the pooled prevalence was 28.6%. Offspring of people with COPD had 1.57 times greater odds (95% confidence interval =1.29–1.93; PCOPD compared with people not having a parental history of COPD. Conclusion The prevalence of COPD in adult offspring of people with COPD is greater than population-based estimates, and the ORs indicate a higher risk in this group. This offers clinicians a potential strategy for opportunistic screening, early identification, and intervention in this at-risk group. PMID:28182144

  2. Maternal corticosterone exposure has transgenerational effects on grand-offspring.

    Science.gov (United States)

    Khan, Nicola; Peters, Richard A; Richardson, Emily; Robert, Kylie A

    2016-11-01

    The hormone fluctuations that an animal experiences during ovulation can have lifelong effects on developing offspring. These hormones may act as an adaptive mechanism, allowing offspring to be 'pre-programmed' to survive in an unstable environment. Here, we used a transgenerational approach to examine the effects of elevated maternal corticosterone (CORT) on the future reproductive success of female offspring. We show that female zebra finches (Taeniopygia guttata) exposed to embryonic CORT produce daughters that have equal reproductive success (clutch sizes, fertility, hatching success) compared with the daughters produced from untreated mothers, but their offspring had accelerated post-hatching growth rates and were significantly heavier by nutritional independence. Although there was no significant effect on primary offspring sex ratio, females from CORT-treated mothers produced significantly female-biased clutches by nutritional independence. To the best of our knowledge, this is the first record of a transgenerational sex ratio bias in response to elevated maternal CORT in any avian species. © 2016 The Author(s).

  3. Maternal high fructose and low protein consumption during pregnancy and lactation share some but not all effects on early-life growth and metabolic programming of rat offspring.

    Science.gov (United States)

    Arentson-Lantz, Emily J; Zou, Mi; Teegarden, Dorothy; Buhman, Kimberly K; Donkin, Shawn S

    2016-09-01

    Maternal nutritional stress during pregnancy acts to program offspring metabolism. We hypothesized that the nutritional stress caused by maternal fructose or low protein intake during pregnancy would program the offspring to develop metabolic aberrations that would be exacerbated by a diet rich in fructose or fat during adult life. The objective of this study was to characterize and compare the fetal programming effects of maternal fructose with the established programming model of a low-protein diet on offspring. Male offspring from Sprague-Dawley dams fed a 60% starch control diet, a 60% fructose diet, or a low-protein diet throughout pregnancy and lactation were weaned onto either a 60% starch control diet, 60% fructose diet, or a 30% fat diet for 15 weeks. Offspring from low-protein and fructose-fed dam showed retarded growth (Pprotein dams (1.31 vs 0.89, 0.85; confidence interval, 0.78-1.04). Similarly, maternal fructose (P=.09) and low-protein (Pprotein restriction such as retarded growth, but is unique in programming of selected hepatic and intestinal transcripts. Copyright © 2016. Published by Elsevier Inc.

  4. Are mothers' and fathers' parenting characteristics associated with emerging adults' academic engagement?

    Science.gov (United States)

    Waterman, Emily A; Lefkowitz, Eva S

    2017-06-01

    Although parenting is clearly linked to academic engagement in adolescence, less is known about links between parenting and academic engagement in emerging adulthood. A diverse sample of college students ( N = 633; 53.1% female, 45.7% White/European American, 28.3% Asian American/Hawaiian/Pacific Islander, 26.4% Hispanic/Latino American, 21.6% Black/African American, and 2.8% Native American/American Indian) answered surveys about mothers' and fathers' parenting style, parent-offspring relationship quality, academic attitudes, academic behaviors, and academic performance. Emerging adults with more permissive mothers viewed grades as less important than emerging adults with less permissive mothers. Mothers' authoritarian parenting, mothers' permissive parenting, and relationship quality with father were differentially related to academic engagement depending on emerging adults' gender. Both mothers' and fathers' parenting characteristics may impact the academic engagement of emerging adults via past parenting behaviors and current quality of the parent-offspring relationship, despite decreased physical proximity of emerging adults and their parents.

  5. Maternal smoking during pregnancy and self-reported delinquency by offspring.

    Science.gov (United States)

    Ellis, Lee; Widmayer, Alan; Das, Shyamal

    2012-12-01

    Several studies have reported significant positive correlations between smoking during pregnancy by mothers and the involvement of their offspring in criminal/delinquent behaviour later in life, but these findings have been described as modest and the criminality based on official conviction statistics. We sought to verify this relationship and probe for more details on the basis of self-reported offending among college students. Independently completed questionnaires were collected from 6332 students and their mothers. The students provided information about their delinquent acts, if any, according to eight categories. Their mothers provided retrospective reports of their smoking habits, if any, during pregnancy. Mothers who recalled having smoked during pregnancy were significantly more likely than non-smoking mothers to have offspring who self-reported engaging in some types of delinquency. This relationship was more evident for female offspring than for male offspring and was most pronounced for illegal drug use by the offspring. There was, however, no relationship between offspring offending and estimated number of cigarettes smoked by mothers, month of pregnancy when smoked or consistency of smoking throughout pregnancy. Overall, our study confirms that maternal smoking during pregnancy is associated with offspring involvement in delinquency, but the lack of critical timing or dose-response relationships between maternal smoking and later offspring delinquency cast doubt on the possibility that the associations are due to teratogenic effects of tobacco smoke. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Paternal care in a fish: epigenetics and fitness enhancing effects on offspring anxiety.

    Science.gov (United States)

    McGhee, Katie E; Bell, Alison M

    2014-11-07

    In many animals, including humans, interactions with caring parents can have long-lasting effects on offspring sensitivity to stressors. However, whether these parental effects impact offspring fitness in nature is often unclear. In addition, despite evidence that maternal care can influence offspring behaviour via epigenetic alterations to the genome, it remains unclear whether paternal care has similar effects. Here, we show in three-spined sticklebacks, a fish in which fathers are the sole provider of offspring care, that the direct care provided by fathers affects offspring anxiety and the potential for epigenetic alterations to the offspring genome. We find that families are differentially vulnerable to early stress and fathers can compensate for this differential sensitivity with the quality of their care. This variation in paternal care is also linked to the expression in offspring brains of a DNA methyltransferase (Dnmt3a) responsible for de novo methylation. We show that these paternal effects are potentially adaptive and anxious offspring are unlikely to survive an encounter with a predator. By supplying offspring care, fathers reduce offspring anxiety thereby increasing the survival of their offspring-not in the traditional sense through resource provisioning but through an epigenetic effect on offspring behavioural development. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  7. Interspecific Interactions and the Scope for Parent-Offspring Conflict: High Mite Density Temporarily Changes the Trade-Off between Offspring Size and Number in the Burying Beetle, Nicrophorus vespilloides.

    Science.gov (United States)

    De Gasperin, Ornela; Kilner, Rebecca M

    2016-01-01

    Parents have a limited amount of resources to invest in reproduction and commonly trade-off how much they invest in offspring size (or quality) versus brood size. A negative relationship between offspring size and number has been shown in numerous taxa and it underpins evolutionary conflicts of interest between parents and their young. For example, previous work on vertebrates shows that selection favours mothers that produce more offspring, at the expense of individual offspring size, yet favours offspring that have relatively few siblings and therefore attain a greater size at independence. Here we analyse how this trade-off is temporarily affected by stochastic variation in the intensity of interspecific interactions. We examined the effect of the mite Poecilochirus carabi on the relationship between offspring size and number in the burying beetle, Nicrophorus vespilloides. We manipulated the initial number of mites in the reproductive event (by introducing either no mites, 4 mites, 10 mites, or 16 mites), and assessed the effect on the brood. We found a similar trade-off between offspring size and number in all treatments, except in the '16 mite' treatment where the correlation between offspring number and size flattened considerably. This effect arose because larvae in small broods failed to attain a high mass by dispersal. Our results show that variation in the intensity of interspecific interactions can temporarily change the strength of the trade-off between offspring size and number. In this study, high densities of mites prevented individual offspring from attaining their optimal weight, thus potentially temporarily biasing the outcome of parent-offspring conflict in favour of parents.

  8. The study on the cephalometric similarity between parents and offspring

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Woo Ghon; Ahn, Hyung Kyu [Department of Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1975-11-15

    The study was performed to investigate cephalometric similarity between parents and offspring of the Korean family by lateral cephalometric analysis. The lateral cephalograms consist of the 8 families comprising 16 parents, 5 sons and 7 daughters. In order to make an investigation of the similarity, 12 measuring points were set up, and 22 linear measurements on each depth, height and 5 angular measurements were made. The author drew up the profilograms to compare parents with offspring in each family group. The obtained results were as follows: 1. There was no common similarity on specific region between parents and offspring in each family group. 2. There was partial similarity between single parent and offspring. 3. The partial similarity between single parent and offspring was noted on the upper face in general.

  9. The study on the cephalometric similarity between parents and offspring

    International Nuclear Information System (INIS)

    Kang, Woo Ghon; Ahn, Hyung Kyu

    1975-01-01

    The study was performed to investigate cephalometric similarity between parents and offspring of the Korean family by lateral cephalometric analysis. The lateral cephalograms consist of the 8 families comprising 16 parents, 5 sons and 7 daughters. In order to make an investigation of the similarity, 12 measuring points were set up, and 22 linear measurements on each depth, height and 5 angular measurements were made. The author drew up the profilograms to compare parents with offspring in each family group. The obtained results were as follows: 1. There was no common similarity on specific region between parents and offspring in each family group. 2. There was partial similarity between single parent and offspring. 3. The partial similarity between single parent and offspring was noted on the upper face in general.

  10. A theoretical model of the evolution of maternal effects under parent-offspring conflict.

    Science.gov (United States)

    Uller, Tobias; Pen, Ido

    2011-07-01

    The evolution of maternal effects on offspring phenotype should depend on the extent of parent-offspring conflict and costs and constraints associated with maternal and offspring strategies. Here, we develop a model of maternal effects on offspring dispersal phenotype under parent-offspring conflict to evaluate such dependence. In the absence of evolutionary constraints and costs, offspring evolve dispersal rates from different patch types that reflect their own, rather than the maternal, optima. This result also holds true when offspring are unable to assess their own environment because the maternal phenotype provides an additional source of information. Consequently, maternal effects on offspring diapause, dispersal, and other traits that do not necessarily represent costly resource investment are more likely to maximize offspring than maternal fitness. However, when trait expression was costly, the evolutionarily stable dispersal rates tended to deviate from those under both maternal and offspring control. We use our results to (re)interpret some recent work on maternal effects and their adaptive value and provide suggestions for future work. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  11. Helpers increase the reproductive potential of offspring in cooperative meerkats

    Science.gov (United States)

    Russell, A.F; Young, A.J; Spong, G; Jordan, N.R; Clutton-Brock, T.H

    2006-01-01

    In both animal and human societies, individuals may forego personal reproduction and provide care to the offspring of others. Studies aimed at investigating the adaptive nature of such cooperative breeding systems in vertebrates typically calculate helper ‘fitness’ from relationships of helper numbers and offspring survival to independence. The aim of this study is to use observations and supplemental feeding experiments in cooperatively breeding meerkats, Suricata suricatta, to investigate whether helpers influence the long-term reproductive potential of offspring during adulthood. We show that helpers have a significant and positive influence on the probability that offspring gain direct reproductive success in their lifetimes. This effect arises because helpers both reduce the age at which offspring begin to reproduce as subordinates and increase the probability that they will compete successfully for alpha rank. Supplemental feeding experiments confirm the causality of these results. Our results suggest that one can neither discount the significance of helper effects when none is found nor necessarily estimate accurately the fitness benefit that helpers accrue, unless their effects on offspring are considered in the long term. PMID:17476771

  12. Maternal effects alter the severity of inbreeding depression in the offspring.

    Science.gov (United States)

    Pilakouta, Natalie; Smiseth, Per T

    2016-09-14

    A maternal effect is a causal influence of the maternal phenotype on the offspring phenotype over and above any direct effects of genes. There is abundant evidence that maternal effects can have a major impact on offspring fitness. Yet, no previous study has investigated the potential role of maternal effects in influencing the severity of inbreeding depression in the offspring. Inbreeding depression is a reduction in the fitness of inbred offspring relative to outbred offspring. Here, we tested whether maternal effects due to body size alter the magnitude of inbreeding depression in the burying beetle Nicrophorus vespilloides We found that inbreeding depression in larval survival was more severe for offspring of large females than offspring of small females. This might be due to differences in how small and large females invest in an inbred brood because of their different prospects for future breeding opportunities. To our knowledge, this is the first evidence for a causal effect of the maternal phenotype on the severity of inbreeding depression in the offspring. In natural populations that are subject to inbreeding, maternal effects may drive variation in inbreeding depression and therefore contribute to variation in the strength and direction of selection for inbreeding avoidance. © 2016 The Author(s).

  13. Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

    Science.gov (United States)

    Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

    2012-10-01

    The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal.

  14. Interspecific Interactions and the Scope for Parent-Offspring Conflict: High Mite Density Temporarily Changes the Trade-Off between Offspring Size and Number in the Burying Beetle, Nicrophorus vespilloides.

    Directory of Open Access Journals (Sweden)

    Ornela De Gasperin

    Full Text Available Parents have a limited amount of resources to invest in reproduction and commonly trade-off how much they invest in offspring size (or quality versus brood size. A negative relationship between offspring size and number has been shown in numerous taxa and it underpins evolutionary conflicts of interest between parents and their young. For example, previous work on vertebrates shows that selection favours mothers that produce more offspring, at the expense of individual offspring size, yet favours offspring that have relatively few siblings and therefore attain a greater size at independence. Here we analyse how this trade-off is temporarily affected by stochastic variation in the intensity of interspecific interactions. We examined the effect of the mite Poecilochirus carabi on the relationship between offspring size and number in the burying beetle, Nicrophorus vespilloides. We manipulated the initial number of mites in the reproductive event (by introducing either no mites, 4 mites, 10 mites, or 16 mites, and assessed the effect on the brood. We found a similar trade-off between offspring size and number in all treatments, except in the '16 mite' treatment where the correlation between offspring number and size flattened considerably. This effect arose because larvae in small broods failed to attain a high mass by dispersal. Our results show that variation in the intensity of interspecific interactions can temporarily change the strength of the trade-off between offspring size and number. In this study, high densities of mites prevented individual offspring from attaining their optimal weight, thus potentially temporarily biasing the outcome of parent-offspring conflict in favour of parents.

  15. Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway

    Directory of Open Access Journals (Sweden)

    Fan Zhang

    2018-05-01

    Full Text Available Objective: Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring. Methods: Female adult Wistar rats were randomly divided into three groups (n = 15 per group: control (CON group, SCH group and overt hypothyroidism (OH group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP and Morris water-maze (MWM test. The protein expression of the p75 neurotrophin receptor (p75NTR, phospho-c-Jun N-terminal kinase (p-JNK, the pro-apoptotic protein p53 and Bax were detected by Western blotting. Results: The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75NTR, p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group. Conclusions: Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex.

  16. Offspring Size and Reproductive Allocation in Harvester Ants.

    Science.gov (United States)

    Wiernasz, Diane C; Cole, Blaine J

    2018-01-01

    A fundamental decision that an organism must make is how to allocate resources to offspring, with respect to both size and number. The two major theoretical approaches to this problem, optimal offspring size and optimistic brood size models, make different predictions that may be reconciled by including how offspring fitness is related to size. We extended the reasoning of Trivers and Willard (1973) to derive a general model of how parents should allocate additional resources with respect to the number of males and females produced, and among individuals of each sex, based on the fitness payoffs of each. We then predicted how harvester ant colonies should invest additional resources and tested three hypotheses derived from our model, using data from 3 years of food supplementation bracketed by 6 years without food addition. All major results were predicted by our model: food supplementation increased the number of reproductives produced. Male, but not female, size increased with food addition; the greatest increases in male size occurred in colonies that made small females. We discuss how use of a fitness landscape improves quantitative predictions about allocation decisions. When parents can invest differentially in offspring of different types, the best strategy will depend on parental state as well as the effect of investment on offspring fitness.

  17. Fetal hyperglycemia changes human preadipocyte function in adult life

    DEFF Research Database (Denmark)

    Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

    2017-01-01

    Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

  18. Explaining risk for suicidal ideation in adolescent offspring of mothers with depression.

    Science.gov (United States)

    Hammerton, G; Zammit, S; Thapar, A; Collishaw, S

    2016-01-01

    It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent-child relationship. Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19-4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent-child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent-child relationship may also be beneficial.

  19. Reproduction of Varroa destructor and offspring mortality in worker and drone brood cells of Africanized honey bees.

    Science.gov (United States)

    Calderón, R A; Ureña, S; van Veen, J W

    2012-04-01

    Varroa destructor is known to be the most serious parasite of Apis mellifera worldwide. In order to reproduce varroa females enter worker or drone brood shortly before the cell is sealed. From March to December 2008, the reproductive rate and offspring mortality (mature and immature stages), focusing on male absence and male mortality of V. destructor, was investigated in naturally infested worker and drone brood of Africanized honey bees (AHB) in Costa Rica. Data were obtained from 388 to 403 single infested worker and drone brood cells, respectively. Mite fertility in worker and drone brood cells was 88.9 and 93.1%, respectively. There was no difference between the groups (X(2) = 3.6, P = 0.06). However, one of the most significant differences in mite reproduction was the higher percentage of mites producing viable offspring in drone cells (64.8%) compared to worker cells (37.6%) (X(2) = 57.2, P drone cells was high in the protonymph stage (mobile and immobile). A significant finding was the high rate of male mortality. The worker and drone brood revealed that 23.9 and 6.9%, respectively, of the adult male offspring was found dead. If the absence (missing) of the male and adult male mortality are taken together the percentage of cells increased to 40.0 and 21.3% in worker and drone cells, respectively (X(2) = 28.8, P < 0.05). The absence of the male or male mortality in a considerable number of worker cells naturally infested with varroa is the major factor in our study which reduces the production of viable daughters in AHB colonies in Costa Rica.

  20. Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

    Science.gov (United States)

    Evangelio, Marian; García-Amado, María; Clascá, Francisco

    2018-01-01

    A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

  1. In Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring

    Directory of Open Access Journals (Sweden)

    Zhengmeng Ye

    2018-03-01

    Full Text Available Background/Aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5 exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R, regulated by G protein-coupled receptor kinase type 4 (GRK4, plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2.5–induced hypertension in the offspring. Methods: Pregnant Sprague–Dawley rats were given an oropharyngeal drip of PM2.5 (1.0 mg/kg at gestation day 8, 10, and 12. The blood pressure, 24-hour sodium excretion, and urine volume were measured in the offspring. The expression levels of GRK4 and D1R were determined by immunoblotting. The phosphorylation of D1R was investigated using immunoprecipitation. Plasma malondialdehyde and superoxide dismutase levels were also measured in the offspring. Results: As compared with saline-treated dams, offspring of PM2.5-treated dams had increased blood pressure, impaired sodium excretion, and reduced D1R-mediated natriuresis and diuresis, accompanied by decreased renal D1R expression and GRK4 expression. The impaired renal D1R function and increased GRK4 expression could be caused by increased reactive oxidative stress (ROS induced by PM2.5 exposure. Administration of tempol, a redox-cycling nitroxide, for 4 weeks in the offspring of PM2.5-treated dam normalized the decreased renal D1R expression and increased renal D1R phosphorylation and GRK4 expression. Furthermore, tempol normalized the increased renal expression of c-Myc, a transcription factor that regulates GRK4 expression. Conclusions: In utero exposure to PM2.5 increases ROS and GRK4 expression, impairs D1R-mediated sodium excretion, and increases blood pressure in the offspring. These studies suggest that normalization of D1R function may be a target for the

  2. Enduring Effects of Paternal Deprivation in California Mice (Peromyscus californicus: Behavioral Dysfunction and Sex-Dependent Alterations in Hippocampal New Cell Survival

    Directory of Open Access Journals (Sweden)

    Erica R. Glasper

    2018-02-01

    Full Text Available Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus. California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1 biparental care: mate pairs remained with their offspring until weaning; or (2 paternal deprivation (PD: paternal males were permanently removed from their home cage on postnatal day (PND 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stress-coping behaviors (i.e., percent time spent immobile during the forced swim task—an effect that was also not sex

  3. Total and Trimester-Specific Gestational Weight Gain and Offspring Birth and Early Childhood Weight: A Prospective Cohort Study on Monozygotic Twin Mothers and Their Offspring.

    Science.gov (United States)

    Scheers Andersson, Elina; Silventoinen, Karri; Tynelius, Per; Nohr, Ellen A; Sørensen, Thorkild I A; Rasmussen, Finn

    2016-08-01

    Gestational weight gain (GWG) has in numerous studies been associated with offspring birth weight (BW) and childhood weight. However, these associations might be explained by genetic confounding as offspring inherit their mother's genetic potential to gain weight. Furthermore, little is known about whether particular periods of pregnancy could influence offspring body weight differently. We therefore aimed to explore total and trimester-specific effects of GWG in monozygotic (MZ) twin mother-pairs on their offspring's BW, weight at 1 year and body mass index (BMI) at 5 and 10 years. MZ twin mothers born 1962-1975 were identified in national Swedish registers, and data on exposure and outcome variables was collected from medical records. We analyzed associations within and between twin pairs. We had complete data on the mothers' GWG and offspring BW for 82 pairs. The results indicated that total, and possibly also second and third trimester GWG were associated with offspring BW within the twin pairs in the fully adjusted model (β = 0.08 z-score units, 95% CI: 0.001, 0.17; β = 1.32 z-score units, 95% CI: -0.29, 2.95; and β = 1.02 z-score units, 95% CI: -0.50, 2.54, respectively). Our findings, although statistically weak, suggested no associations between GWG and offspring weight or BMI during infancy or childhood. Our study suggests that total, and possibly also second and third trimester, GWG are associated with offspring BW when taking shared genetic and environmental factors within twin pairs into account. Larger family-based studies with long follow-up are needed to confirm our findings.

  4. Gene expression of drug metabolizing enzymes in adult and aged mouse liver: A modulation by immobilization stress

    International Nuclear Information System (INIS)

    Mikhailova, O.N.; Gulyaeva, L.F.; Filipenko, M.L.

    2005-01-01

    The role of stress in the regulation of enzymatic systems involved in the biotransformation of xenobiotics, as well as endogenous substrates in the liver was investigated using single immobilization stress as a model. Adult (3 months of age) and aged (26 months) C3H/a male mice were used. Cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2), glutathione S-transferase M1 (GSTM1), aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and catechol-O-methyltransferase (COMT) mRNA levels in the mouse liver were measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Excluding CYP1A1, experiments revealed significant differences in the expression of these genes between adult- and aged-control animals. The influence of stress on the expression of genes studied was shown to be higher in adult mice than in aged ones. Our results clearly demonstrate the lack of response or even the attenuation of gene expression in aged animals that may play an important role in age-related pathologies and diseases

  5. A model for optimal offspring size in fish, including live-bearing and parental effects.

    Science.gov (United States)

    Jørgensen, Christian; Auer, Sonya K; Reznick, David N

    2011-05-01

    Since Smith and Fretwell's seminal article in 1974 on the optimal offspring size, most theory has assumed a trade-off between offspring number and offspring fitness, where larger offspring have better survival or fitness, but with diminishing returns. In this article, we use two ubiquitous biological mechanisms to derive the shape of this trade-off: the offspring's growth rate combined with its size-dependent mortality (predation). For a large parameter region, we obtain the same sigmoid relationship between offspring size and offspring survival as Smith and Fretwell, but we also identify parameter regions where the optimal offspring size is as small or as large as possible. With increasing growth rate, the optimal offspring size is smaller. We then integrate our model with strategies of parental care. Egg guarding that reduces egg mortality favors smaller or larger offspring, depending on how mortality scales with size. For live-bearers, the survival of offspring to birth is a function of maternal survival; if the mother's survival increases with her size, then the model predicts that larger mothers should produce larger offspring. When using parameters for Trinidadian guppies Poecilia reticulata, differences in both growth and size-dependent predation are required to predict observed differences in offspring size between wild populations from high- and low-predation environments.

  6. Characterization of piRNAs across postnatal development in mouse brain

    KAUST Repository

    Ghosheh, Yanal; Seridi, Loqmane; Ryu, Tae Woo; Takahashi, Hazuki; Orlando, Valerio; Carninci, Piero; Ravasi, Timothy

    2016-01-01

    PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues– where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.

  7. Characterization of piRNAs across postnatal development in mouse brain

    KAUST Repository

    Ghosheh, Yanal

    2016-04-26

    PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues– where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.

  8. Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers.

    Science.gov (United States)

    Leveque, Lucie; Hodgson, Samantha; Peyton, Stephen; Koyama, Motoko; MacDonald, Kelli P A; Khosrotehrani, Kiarash

    2014-05-01

    The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  9. In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra

    2013-01-01

    Inhalation of particles has been shown to induce mutations in the male germline in mice following both prenatal and adult exposures in several experiments. In contrast, the effects of particles on female germ cell mutagenesis are not well established. Germline mutations are induced during active...... cell division, which occurs during fetal development in females. We investigated the effects of prenatal exposure to carbon black nanoparticles (CB) on induction of mutations in the female mouse germline during fetal development, spanning the critical developmental stages of oogenesis. Pregnant C57BL/6...... mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring....

  10. Insect parents improve the anti-parasitic and anti-bacterial defence of their offspring by priming the expression of immune-relevant genes.

    Science.gov (United States)

    Trauer-Kizilelma, Ute; Hilker, Monika

    2015-09-01

    Insect parents that experienced an immune challenge are known to prepare (prime) the immune activity of their offspring for improved defence. This phenomenon has intensively been studied by analysing especially immunity-related proteins. However, it is unknown how transgenerational immune priming affects transcript levels of immune-relevant genes of the offspring upon an actual threat. Here, we investigated how an immune challenge of Manduca sexta parents affects the expression of immune-related genes in their eggs that are attacked by parasitoids. Furthermore, we addressed the question whether the transgenerational immune priming of expression of genes in the eggs is still traceable in adult offspring. Our study revealed that a parental immune challenge did not affect the expression of immune-related genes in unparasitised eggs. However, immune-related genes in parasitised eggs of immune-challenged parents were upregulated to a higher level than those in parasitised eggs of unchallenged parents. Hence, this transgenerational immune priming of the eggs was detected only "on demand", i.e. upon parasitoid attack. The priming effects were also traceable in adult female progeny of immune-challenged parents which showed higher transcript levels of several immune-related genes in their ovaries than non-primed progeny. Some of the primed genes showed enhanced expression even when the progeny was left unchallenged, whereas other genes were upregulated to a greater extent in primed female progeny than non-primed ones only when the progeny itself was immune-challenged. Thus, the detection of transgenerational immune priming strongly depends on the analysed genes and the presence or absence of an actual threat for the offspring. We suggest that M. sexta eggs laid by immune-challenged parents "afford" to upregulate the transcription of immunity-related genes only upon attack, because they have the chance to be endowed by parentally directly transferred protective proteins

  11. Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease.

    Science.gov (United States)

    Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

    2008-05-01

    Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

  12. Maternal pre-pregnancy BMI and offspring body composition in young adulthood: the modifying role of offspring sex and birth order.

    Science.gov (United States)

    Chaparro, M Pia; Koupil, Ilona; Byberg, Liisa

    2017-12-01

    To investigate if the association between maternal pre-pregnancy BMI and offspring's body composition in late adolescence and young adulthood varies by offspring birth order and sex. Family cohort study, with data from registers, questionnaires and physical examinations. The main outcome under study was offspring body composition (percentage fat mass (%FM), percentage lean mass (%LM)) measured by dual-energy X-ray absorptiometry. Uppsala, Sweden. Two hundred and twenty-six siblings (first-born v. second-born; average age 19 and 21 years) and their mothers. In multivariable linear regression models, maternal pre-pregnancy BMI was positively associated with daughter's %FM, with stronger estimates for first-born (β=0·97, 95 % CI 0·14, 1·80) v. second-born daughters (β=0·64, 95 % CI 0·08, 1·20). Mother's BMI before her first pregnancy was associated with her second-born daughter's body composition (β=1·05, 95 % CI 0·31, 1·79 (%FM)) Similar results albeit in the opposite direction were observed for %LM. No significant associations were found between pre-pregnancy BMI and %FM (β=0·59, 95 % CI-0·27, 1·44 first-born; β=-0·13, 95 % CI-0·77, 0·52 second-born) or %LM (β=-0·54, 95 % CI-1·37, 0·28 first-born; β=0·11, 95 % CI-0·52, 0·74 second-born) for sons. A higher pre-pregnancy BMI was associated with higher offspring %FM and lower offspring %LM in late adolescence and young adulthood, with stronger associations for first-born daughters. Preventing obesity at the start of women's reproductive life might reduce the risk of obesity in her offspring, particularly for daughters.

  13. Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

    Science.gov (United States)

    Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

    2017-11-01

    Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and

  14. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2016-09-01

    Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Maternal dietary patterns during pregnancy in relation to offspring forearm fractures

    DEFF Research Database (Denmark)

    Petersen, Sesilje Elise Bondo; Rasmussen, Morten Arendt; Olsen, Sjurdur F

    2015-01-01

    Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish...... associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future...

  16. Capturing Between- and Within-Family Differences in Parental Support to Adult Children: A Typology Approach.

    Science.gov (United States)

    Kim, Kyungmin; Fingerman, Karen L; Birditt, Kira S; Zarit, Steven H

    2016-11-01

    Families differ widely in the support they provide to adult offspring, both with regard to the overall level as well as the extent to which support is evenly distributed across offspring. This study addressed these dynamics by creating family profiles based on the average level and differentiation of support among children. We also examined demographic and psychological factors that predict typology membership. We utilized data from 431 middle-aged parents (aged 40-60) with at least two adult children. Parents provided separate ratings of support given to each child. Latent profile analysis was applied to two indicators of within-family support: mean level and differentiation among offspring. Latent profile analysis identified four patterns of parental support: (a) high support-low differentiation (52%), (b) medium support-high differentiation (26%), (c) low support-low differentiation (17%), and (d) low support-very high differentiation (5%). These patterns reflected distinct family characteristics, such as parental resources, parental beliefs (i.e., equal treatment, obligation), and offspring characteristics. Our findings emphasize the need to capture dynamics of support exchanges among multiple offspring at the level of family. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

    Science.gov (United States)

    Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

    2015-01-01

    The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

  18. Parental effects alter the adaptive value of an adult behavioural trait.

    Science.gov (United States)

    Kilner, Rebecca M; Boncoraglio, Giuseppe; Henshaw, Jonathan M; Jarrett, Benjamin J M; De Gasperin, Ornela; Attisano, Alfredo; Kokko, Hanna

    2015-09-22

    The parents' phenotype, or the environment they create for their young, can have long-lasting effects on their offspring, with profound evolutionary consequences. Yet, virtually no work has considered how such parental effects might change the adaptive value of behavioural traits expressed by offspring upon reaching adulthood. To address this problem, we combined experiments on burying beetles (Nicrophorus vespilloides) with theoretical modelling and focussed on one adult behavioural trait in particular: the supply of parental care. We manipulated the early-life environment and measured the fitness payoffs associated with the supply of parental care when larvae reached maturity. We found that (1) adults that received low levels of care as larvae were less successful at raising larger broods and suffered greater mortality as a result: they were low-quality parents. Furthermore, (2) high-quality males that raised offspring with low-quality females subsequently suffered greater mortality than brothers of equivalent quality, which reared larvae with higher quality females. Our analyses identify three general ways in which parental effects can change the adaptive value of an adult behavioural trait: by influencing the associated fitness benefits and costs; by consequently changing the evolutionary outcome of social interactions; and by modifying the evolutionarily stable expression of behavioural traits that are themselves parental effects.

  19. Two Y genes can replace the entire Y chromosome for assisted reproduction in the mouse.

    Science.gov (United States)

    Yamauchi, Yasuhiro; Riel, Jonathan M; Stoytcheva, Zoia; Ward, Monika A

    2014-01-03

    The Y chromosome is thought to be important for male reproduction. We have previously shown that, with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Here, we demonstrate that live mouse progeny can also be generated by using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y. Sry is believed to function primarily in sex determination during fetal life. Eif2s3y may be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. Our findings are relevant, but not directly translatable, to human male infertility cases.

  20. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

    Directory of Open Access Journals (Sweden)

    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal