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Sample records for female rat offspring

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

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    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

  2. Maternal omega-3 supplementation increases fat mass in male and female rat offspring

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    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

  3. Bisphenol A induces oxidative stress and DNA damage in hepatic tissue of female rat offspring

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    Jehane I. Eid

    2015-08-01

    Full Text Available Bisphenol A (BPA is an endocrine disrupting compound widely spread in our living environment. It is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to the limited information concerning the effect of BPA on the liver, the present study was designed to assess hepatic tissue injury induced by early life exposure to BPA in female rat offspring. Rat dams (n = 9 were gavaged with 0.5 and 50 mg of BPA/kg b.w./day throughout lactation until weaning. The sham group received olive oil for the same duration while the control group did not receive any injection. The liver tissue was collected from female pups at different pubertal periods (PND50, 90 and 110 to evaluate oxidative stress biomarkers, extent of DNA damage and histopathological changes. Our results indicated that early life exposure to BPA significantly increased oxidative/nitrosative stress, decreased antioxidant enzyme activities, induced DNA damage and chronic severe inflammation in the hepatic tissue in a time dependent manner. These data suggested that BPA causes long-term adverse effects on the liver, which leads to deleterious effects in the liver of female rat offspring.

  4. High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring

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    Pedro S. P. Huot

    2013-01-01

    Full Text Available Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol or 10-fold higher folic acid (HFol amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P=0.03 and, after adjusting for body weight and femoral length, smaller femoral area (2%, P=0.03, compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P=0.01 and density (4%, P=0.002 of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P=0.01 and stiffness (P=0.002. However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

  5. Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

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    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.

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

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    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.

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

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    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

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

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    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

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

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    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.

  10. Maternal swimming exercise during pregnancy attenuates anxiety/depressive-like behaviors and voluntary morphine consumption in the pubertal male and female rat offspring born from morphine dependent mothers.

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    Torabi, Masoumeh; Pooriamehr, Alireza; Bigdeli, Imanollah; Miladi-Gorji, Hossein

    2017-10-17

    This study was designed to examine whether maternal swimming exercise during pregnancy would attenuate prenatally morphine-induced anxiety, depression and voluntary consumption of morphine in the pubertal male and female rat offspring. Pregnant rats during the development of morphine dependence were allowed to swim (30-45min/d, 3days per a week) on gestational days 11-18. Then, the pubertal male and female rat offspring were tested for the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that male and female rat offspring born of the swimmer morphine-dependent mothers exhibited an increase in EPM open arm time and entries, higher levels of sucrose preference than their sedentary control mothers. Voluntary consumption of morphine was less in the male and female rat offspring born of the swimmer morphine-dependent mothers as compared with their sedentary control mothers during three periods of the intake of drug. Thus, swimming exercise in pregnant morphine dependent mothers decreased anxiety, depressive-like behavior and also the voluntary morphine consumption in the pubertal male and female offspring, which may prevent prenatally morphine-induced behavioral sensitization in offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Maternal High Fat Feeding Does Not Have Long-Lasting Effects on Body Composition and Bone Health in Female and Male Wistar Rat Offspring at Young Adulthood

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    Paula M. Miotto

    2013-12-01

    Full Text Available High fat diets adversely affect body composition, bone mineral and strength, and alter bone fatty acid composition. It is unclear if maternal high fat (HF feeding permanently alters offspring body composition and bone health. Female rats were fed control (CON or HF diet for 10 weeks, bred, and continued their diets throughout pregnancy and lactation. Male and female offspring were studied at weaning and 3 months, following consumption of CON diet. At weaning, but not 3 months of age, male and female offspring from dams fed HF diet had lower lean mass and higher fat and bone mass, and higher femur bone mineral density (females only than offspring of dams fed CON diet. Male and female offspring femurs from dams fed HF diet had higher monounsaturates and lower n6 polyunsaturates at weaning than offspring from dams fed CON diet, where females from dams fed HF diet had higher saturates and lower n6 polyunsaturates at 3 months of age. There were no differences in strength of femurs or lumbar vertebrae at 3 months of age in either male or female offspring. In conclusion, maternal HF feeding did not permanently affect body composition and bone health at young adulthood in offspring.

  12. Effects on reproduction in female offspring from Sprague-Dawley rats fed 10% snakeweed (Gutierrezia microcephala) throughout pregnancy and concurrent treatment with safflower oil.

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    Staley, E C; Smith, G S; Greenberg, J A

    1995-10-01

    Previous studies determined that safflower oil administration provided protection against the embryotoxicity seen following ingestion of 10% snakeweed (Gutierrezia microcephala) throughout pregnancy. Sixty-two young primiparous female rats born in those studies were paired with adult male Sprague-Dawley rats. After 4 d they were removed and carried their litters to term. Observations were made of the presence and extent of reproductive effects attributable to the 10% snakeweed exposure and differences in fecundity that were attributable to dosing with safflower oil or normal saline during the snakeweed exposure. Of the 62 rats, 50 carried litters to term and approximated the reproductive efficiency of normal primiparous Sprague-Dawley rats. There was no significant difference between the fecundity of females born to rats fed the 10% snakeweed and dosed with safflower oil, those born of rats fed snakeweed dosed with normal saline, or those fed a snakeweed-free diet and dosed with normal saline. Regardless of the diet or treatment administered, dams carrying their litters to parturition gave birth to healthy, normo-reproductive offspring. While the toxic principles in Gutierrezia species plants may act as estrogenic or anti-estrogenic compounds, they did not impair fertility in the female offspring of dosed rats.

  13. Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

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    Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

    2015-01-01

    BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

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

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    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.

  15. Influence of beryllium chloride and oxide on the sexual function in female rats and development of offspring

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    Selivanova, L.N.; Savinova, T.B.

    1989-11-01

    A translation is given of a Russian article on the influence of beryllium chloride and oxide on the sexual cycle in female rats and on their capacity to conceive; another aim was to identify any embryotoxic and teratogenic effect of these compounds and to identify the exposure period values for pregnant females and the capacity of beryllium to penetrate the placenta and to accumulate in the foetus. (UK)

  16. Effect of Cell-Phone Radiation in Pregnancy on Serum Levels of Sexual Hormones and Dynastic Cells in adult Female Offspring in Rats

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    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

  17. Omega-3 attenuates high fat diet-induced kidney injury of female rats and renal programming of their offsprings.

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    Shamseldeen, Asmaa Mohammed; Ali Eshra, Mohammed; Ahmed Rashed, Laila; Fathy Amer, Marwa; Elham Fares, Amal; Samir Kamar, Samaa

    2018-05-09

    Maternal diet composition could influence fetal organogenesis. We investigated effects of high fat diet (HFD) intake alone or combined with omega 3 during pregnancy, lactation and early days of weaning on nephrogenesis of pups and maternal renal function and morphology. Mothers and their pups included in each group were supplied with the same diet composition. Rats were divided into group I, II and III supplied with chow of either 10 kcal%, 45 kcal% or 45 kcal% from fat together with omega-3 respectively. Group II showed increased serum urea and creatinine, renal TNF-α, IL1β. Structural injury was observed in mothers and their pups as Bowman's capsule and tubular dilatation and increased expression of PCNA that were decreased following omega-3 supplementation added to down regulation of Wnt4, Pax2 gene and podocin expression. Omega-3 supplementation improves lipid nephrotoxicity observed in mothers and their pups.

  18. A maternal high-protein diet predisposes female offspring to increased fat mass in adulthood whereas a prebiotic fibre diet decreases fat mass in rats.

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    Hallam, Megan C; Reimer, Raylene A

    2013-11-14

    The negative effects of malnourishment in utero have been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HP v. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood.

  19. [Pituitary function of dysgenesic femal rats. Studies with grafting method].

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    Vanhems, E; Busquet, J

    1975-01-01

    Misulban administered to pregnant rats on the 15th day of gestation provoked gonadal dysgenesia in the offspring. Study of the pituitary function of dysgenesic female rats, realized by grafting method, showed gonadotrophic hypersecretion.

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

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    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.

  1. Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

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    Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

    2013-06-25

    Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    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.

  5. Maternal Rat Diabetes Mellitus Deleteriously Affects Insulin Sensitivity and Beta-Cell Function in the Offspring

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    Abdel-Baset M. Aref

    2013-01-01

    Full Text Available This study was designed to assess the effect of maternal diabetes in rats on serum glucose and insulin concentrations, insulin resistance, histological architecture of pancreas and glycogen content in liver of offspring. The pregnant rat females were allocated into two main groups: normal control group and streptozotocin-induced diabetic group. After birth, the surviving offspring were subjected to biochemical and histological examination immediately after delivery and at the end of the 1st and 2nd postnatal weeks. In comparison with the offspring of normal control dams, the fasting serum glucose level of offspring of diabetic mothers was significantly increased at the end of the 1st and 2nd postnatal weeks. Serum insulin level of offspring of diabetic dams was significantly higher at birth and decreased significantly during the following 2 postnatal weeks, while in normal rat offspring, it was significantly increased with progress of time. HOMA Insulin Resistance (HOMA-IR was significantly increased in the offspring of diabetic dams at birth and after 1 week than in normal rat offspring, while HOMA insulin sensitivity (HOMA-IS was significantly decreased. HOMA beta-cell function was significantly decreased at all-time intervals in offspring of diabetic dams. At birth, islets of Langerhans as well as beta cells in offspring of diabetic dams were hypertrophied. The cells constituting islets seemed to have a high division rate. However, beta-cells were degenerated during the following 2 post-natal weeks and smaller insulin secreting cells predominated. Vacuolation and necrosis of the islets of Langerhans were also observed throughout the experimental period. The carbohydrate content in liver of offspring of diabetic dams was at all-time intervals lower than that in control. The granule distribution was more random. Overall, the preexisting maternal diabetes leads to glucose intolerance, insulin resistance, and impaired insulin sensitivity and

  6. Effects of Buchenavia tomentosa consumption on female rats and their offspring - doi: 10.4025/actascibiolsci.v32i4.7220 Effects of Buchenavia tomentosa consumption on female rats and their offspring - doi: 10.4025/actascibiolsci.v32i4.7220

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    Viviane Mayumi Maruo

    2010-11-01

    Full Text Available Buchenavia tomentosa Eichler is a common plant in Brazilian cerrado. Fruits of this plant are employed in human feeding and folk medicine. Cattle producers affirm that consumption of the fruits cause abortion in cows, and even death. Considering that the plant may be consumed by pregnant women and animals, the present study was undertaken to evaluate the possible toxic effects of the ingestion of B. tomentosa fruit (10% added to the diet, from the first to the twenty-first days of gestation, on reproductive parameters and on physical and neurobehavioral development of rats offspring. An increase in food consumption at pregnancy days 11 and 17, and weight increase at day 17 of pregnancy were observed. Besides that, we verified an increase in weight of male offspring on post natal day 1. Other parameters were not affected by plant consumption. These results indicate that the consumption of B. tomentosa at 10% during pregnancy cause slight toxicological effects. The changes verified in the present study indicate toxic action of the fruit possibly induced by flavonoids with hormonal action; however, further studies must be accomplished to corroborate this hypothesis.Buchenavia tomentosa Eichler is a common plant in Brazilian cerrado. Fruits of this plant are employed in human feeding and folk medicine. Cattle producers affirm that consumption of the fruits cause abortion in cows, and even death. Considering that the plant may be consumed by pregnant women and animals, the present study was undertaken to evaluate the possible toxic effects of the ingestion of B. tomentosa fruit (10% added to the diet, from the first to the twenty-first days of gestation, on reproductive parameters and on physical and neurobehavioral development of rats offspring. An increase in food consumption at pregnancy days 11 and 17, and weight increase at day 17 of pregnancy were observed. Besides that, we verified an increase in weight of male offspring on post natal day 1

  7. Effects of Buchenavia tomentosa consumption on female rats and their offspring = Efeitos do consumo de Buchenavia tomentosa em ratas e em suas proles

    Directory of Open Access Journals (Sweden)

    Viviane Mayumi Maruo

    2010-10-01

    Full Text Available Buchenavia tomentosa Eichler is a common plant in Brazilian cerrado. Fruits of this plant are employed in human feeding and folk medicine. Cattle producers affirm that consumption of the fruits cause abortion in cows, and even death. Considering that the plant may be consumed by pregnant women and animals, the present study was undertaken toevaluate the possible toxic effects of the ingestion of B. tomentosa fruit (10% added to the diet, from the first to the twenty-first days of gestation, on reproductive parameters and on physical and neurobehavioral development of rats offspring. An increase in food consumption at pregnancy days 11 and 17, and weight increase at day 17 of pregnancy were observed. Besides that, we verified an increase in weight of male offspring on post natal day 1. Other parameterswere not affected by plant consumption. These results indicate that the consumption of B. tomentosa at 10% during pregnancy cause slight toxicological effects. The changes verified in the present study indicate toxic action of the fruit possibly induced by flavonoids with hormonal action; however, further studies must be accomplished to corroborate this hypothesis. Buchenavia tomentosa Eichler é uma planta típica do cerrado brasileiro. Os frutos desta planta são empregados na alimentação humana e medicina popular. Criadores de bovinos afirmam que oconsumo desta planta produz aborto em vacas bem como a morte destes animais. Uma vez que a planta pode ser consumida pelo homem e animais, em idade fértil e inclusive gestantes, o presente estudo avaliou os possíveis efeitos tóxicos da ingestão de dieta com 10% de frutos de B. tomentosa do primeiro ao vigésimo primeiro dia de gestação sobre os parâmetros reprodutivos e sobre o desenvolvimento físico e neurocomportamental das ninhadas de ratos. Foram observadaselevações no consumo de alimentos nos dias 11 e 17 de gestação e no peso ao dia 17 de gestação. Aumento do peso dos filhotes

  8. 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.

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

    Science.gov (United States)

    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.

  10. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    Science.gov (United States)

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring. © 2015 Blackwell Verlag GmbH.

  11. Effect of administration of lead nitrate to pregnant rats on the lungs in their offspring.

    Science.gov (United States)

    Lebed'ko, O A; Ryzhavskii, B Ya

    2005-06-01

    Lead nitrate in a dose of 200 mg/kg was administered to female rats via a gartric tube on days 5 and 12 of pregnancy. The lungs of their offspring were examined on day 40 of life. We found a decrease in the ratio between the specific volumes of alveolar lumens and interalveolar septa and hypertrophy of lymphoid tissue in the bronchial wall (compared to the offspring of intact females). Chemiluminescent analysis revealed activation of lipid peroxidation and decrease in antioxidant antiradical activity of the lungs.

  12. IMMUNITY STATE IN THE OFFSPRING OF RATS EXPOSED ANTIGENS TOXOPLASMA GONDII

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    T. F. Sokolova

    2014-01-01

    Full Text Available Today the questions about possibility of development disturbances in the immune system of the fetus and the newborn in chronic toxoplasmosis are poorly understood. Aim of research: to detect immunological disturbances in the offspring of rats which have been administered antigens T. gondii.Two series of experiments was performed. In these experiments white female Wistar rats in the III trimester of pregnancy have been administered corpuscular antigen T. gondii. The 60 days-old offspring of these rats have been included in study group of 137 animals. CD3+ cells count was performed in peripherical blood and standard suspension of splenocytesrats offspring. Peripherical blood cells count was performed in the blood of the rats offspring. In the second experiment rats offspring have been administered sheep erythrocytes in 5 days, before euthanasia. In spleen of this rats antigen-produced cells was counted.In control group was included 118 animals, which was born from white female Wistar rats have been administered 0,9% NaCl solution. CD3+ cells was detected in Cytomics FC500 flow cytometry analyzer (Beckman Coulter,USA by use rats origne-specifed monoclonal antibodies Anti-Rat CD3-FITC (Beckman Coulter,USA. Hematological parameters was assessed by use hematological analyzer Excell-22 (USA.We observed, that CD3+ lymphocytes and antigen-produced cells was decreased in test group (degress of decrease CD3+ cells was 17,2%; р = 0,003 in spleen vs. control group, degress of decrease antigen-produced cells was 27,3%; р = 0,03 vs. control group. Number of leukocytes was increased in in test group (34,5%; р = 0,009 vs. control group. Power and strength correlation pleiades between studied blood and spenal markers were higher in in test group vs. control group (∑Gi = 16; ∑Di = 4,38 vs. ∑Gi = 13; ∑Di = 2,28. This phenomenon is probably due to the development adaptive reactions disruption in the immune system and development

  13. 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.

  14. Effects of paternal obesity on growth and adiposity of male rat offspring.

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    Lecomte, Virginie; Maloney, Christopher A; Wang, Kristy W; Morris, Margaret J

    2017-02-01

    Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk. Copyright © 2017 the American Physiological Society.

  15. Consuming a low-fat diet from weaning to adulthood reverses the programming of food preferences in male, but not in female, offspring of 'junk food'-fed rat dams.

    Science.gov (United States)

    Ong, Z Y; Muhlhausler, B S

    2014-01-01

    This study aimed to determine whether the negative effects of maternal 'junk food' feeding on food preferences and gene expression in the mesolimbic reward system could be reversed by weaning the offspring onto a low-fat diet. Offspring of control (n = 11) and junk food-fed (JF, n = 12) dams were weaned onto a standard rodent chow until 6 weeks (juvenile) or 3 months (adult). They were then given free access to both chow and junk food for 3 weeks and food preferences determined. mRNA expression of key components of the mesolimbic reward system was determined by qRT-PCR at 6 weeks, 3 and 6 months of age. In the juvenile group, both male and female JF offspring consumed more energy and carbohydrate during the junk food exposure at 6 weeks of age and had a higher body fat mass at 3 months (P junk food; however, female JF offspring had a higher body fat mass at 6 months (P junk food exposure on food preferences and fat mass can be reversed by consuming a low-fat diet from weaning to adulthood in males. Females, however, retain a higher propensity for diet-induced obesity even after consuming a low-fat diet for an extended period after weaning. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  16. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    Science.gov (United States)

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques. © The Author(s) 2014.

  17. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring

    OpenAIRE

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    Background The mother?s consumption of high-fat food can affect glucose metabolism and the hypothalamic?pituitary?adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Methods Female rats were randomly divided into normal and high-fat diet groups and were fed in a...

  18. [Effects of in utero exposure to di(2-ethylhexyl) phthalate on sexual development in female offspring].

    Science.gov (United States)

    Ding, Yu; Gao, Yu; Shi, Rong; Zhou, Yi-Jun; Tian, Ying

    2010-02-01

    To evaluate the ability of di(2-ethylhexyl) phthalate (DEHP) with inducing damage in sexual development of female offspring rats after maternal exposure. On gestational day (GD) 12, pregnant Wistar rats were weighed, encoded and randomly assigned to 5 groups (10 dams per group). From GD 12 through GD 17 each dam was dosed daily by gavage with either corn oil (vehicle control, 1 mgxkg(-1)xd(-1)) or DEHP (1, 250, 750 and 1000 mgxkg(-1)xd(-1)). Then female offspring were monitored for eye opening on postnatal day (PND) 14-17, organ coefficient on PND 22 and the time to vaginal opening on PND 30 - 38 (if vagina did not open during the period, observation time should extent to adult), as well as body weight, time to first estrus. No significant changes were observed on eye opening at any dose, which were (15.8 +/- 0.4) d, (16.3 +/- 0.6) d, (16.0 +/- 0.6) d, (15.9 +/- 0.6) d, (15.8 +/- 0.4) d respectively in control, 1, 250, 750 and 1000 mgxkg(-1)xd(-1) (F = 1.363, P = 0.262). However, 62.50% (15/24), 81.25% (26/32) female offspring were permanently absence of vaginal orifice in 750 and 1000 mgxkg(-1)xd(-1) groups respectively, while control, 1 and 250 mgxkg(-1)xd(-1) groups developed normally with vaginal orifices (chi(2) values were 84.92, 132.79, respectively, P xd(-1). After covariance adjustment for body weight, which can statistically influenced the age of vaginal opening (F = 40.857, P xd(-1) group was advanced than control (t = -2.056, P < 0.05). Exposure to DEHP in utero from GD 12 - 17 can result in abnormalities of sexual development such as the time to vaginal opening and vaginal atresia.

  19. Female bluethroats enhance offspring immunocompetence through extra-pair copulations.

    Science.gov (United States)

    Johnsen, A; Andersen, V; Sunding, C; Lifjeld, J T

    2000-07-20

    Female birds frequently copulate with extra-pair males, but the adaptive value of this behaviour is poorly understood. Some studies have suggested that 'good genes' may be involved, where females seek to have their eggs fertilized by high-quality males without receiving any material benefits from them. Nevertheless, it remains to be shown that a genetic benefit is passed on to offspring. Here we report that nestling bluethroats, Luscinia svecica, sired by extra-pair males had a higher T-cell-mediated immune response than their maternal half-siblings raised in the same nest. The difference could not be attributed to nestling body mass, sex or hatching order, but may be an effect of paternal genotype. Extra-pair young were also more immunocompetent than their paternal half-sibs raised in the genetic father's own nest, which indicates an additional effect of maternal genotype. Our results are consistent with the idea that females engage in extra-pair copulations to obtain compatible viability genes, rather than 'good genes' per se.

  20. Offspring predisposition to obesity due to maternal-diet-induced obesity in rats is preventable by dietary normalization before mating.

    Science.gov (United States)

    Castro, Heriberto; Pomar, Catalina Amadora; Palou, Andreu; Picó, Catalina; Sánchez, Juana

    2017-03-01

    We studied in rats whether the expected detrimental effects in offspring associated to maternal dietary obesity may be reverted by obesogenic diet removal 1 month before mating. Female rats were fed a cafeteria diet (CD) from days 10 to 100 and then a standard diet (SD) (postcafeteria rats). One month after CD removal, postcafeteria rats and a group of SD-fed female rats (controls) were mated with males. At weaning, offspring were fed SD and followed until 4 months old. CD was effective at inducing obesity in dams. Its removal led to a reduction in body weight, although, after 30 days, rats retained excess body weight and fat than controls. During lactation, postcafeteria dams showed greater body fat, and higher leptin and adiponectin levels in milk than controls. From 2 months of life, offspring of postcafeteria dams displayed lower body weight than controls, with no differences in the percentage of fat, homeostatic model assessment for insulin resistance, or circulating parameters. Removal of CD in obese rats before gestation, although without complete reversion of body weight excess, may prevent the expected detrimental effects in offspring associated to an excess fat accumulation in adulthood and the related metabolic disturbances. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. 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.

  2. 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.

  3. Role of amygdala kisspeptin in pubertal timing in female rats.

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    Daniel A Adekunbi

    Full Text Available To investigate the mechanism by which maternal obesity disrupts reproductive function in offspring, we examined Kiss1 expression in the hypothalamic arcuate (ARC and anteroventral periventricular (AVPV nuclei, and posterodorsal medial amygdala (MePD of pre-pubertal and young adult offspring. Sprague-Dawley rats were fed either a standard or energy-dense diet for six weeks prior to mating and throughout pregnancy and lactation. Male and female offspring were weaned onto normal diet on postnatal day (pnd 21. Brains were collected on pnd 30 or 100 for qRT-PCR to determine Kiss1 mRNA levels. Maternal obesity increased Kiss1 mRNA expression in the MePD of pre-pubertal male and female offspring, whereas Kiss1 expression was not affected in the ARC or AVPV at this age. Maternal obesity reduced Kiss1 expression in all three brain regions of 3 month old female offspring, but only in MePD of males. The role of MePD kisspeptin on puberty, estrous cyclicity and preovulatory LH surges was assessed directly in a separate group of post-weanling and young adult female rats exposed to a normal diet throughout their life course. Bilateral intra-MePD cannulae connected to osmotic mini-pumps for delivery of kisspeptin receptor antagonist (Peptide 234 for 14 days were chronically implanted on pnd 21 or 100. Antagonism of MePD kisspeptin delayed puberty onset, disrupted estrous cyclicity and reduced the incidence of LH surges. These data show that the MePD plays a key role in pubertal timing and ovulation and that maternal obesity may act via amygdala kisspeptin signaling to influence reproductive function in the offspring.

  4. 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.

  5. Preconception Prebiotic and Sitagliptin Treatment in Obese Rats Affects Pregnancy Outcomes and Offspring Microbiota, Adiposity, and Glycemia

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    Carol A. Dennison

    2017-10-01

    Full Text Available Maternal obesity is associated with increased risk of pregnancy complications and greater risk of obesity in offspring, but studies designed to examine preconception weight loss are limited. The objective of this study was to determine if a combined dietary [oligofructose (OFS] and pharmacological (sitagliptin preconception intervention could mitigate poor pregnancy outcomes associated with maternal obesity and improve offspring metabolic health and gut microbiota composition. Diet-induced obese female Sprague-Dawley rats were randomized to one of four intervention groups for 8 weeks: (1 Obese-Control (consumed control diet during intervention; (2 Obese-OFS (10% OFS diet; (3 Obese-S (sitagliptin drug; (4 Obese-OFS + S (combination treatment. Two reference groups were also included: (5 Obese-HFS (untreated obese consumed high fat/sucrose diet throughout study; (6 Lean-Control (lean reference group that were never obese and consumed control diet throughout. Offspring consumed control diet until 11 weeks of age followed by HFS diet until 17 weeks of age. The Obese-OFS + S rats lost weight during the intervention phase whereas the OFS and S treatments attenuated weight gain compared with Obese-HFS (p < 0.05. Gestational weight gain was lowest in Obese-OFS + S rats and highest in Obese-HFS rats (p < 0.05. Prepregnancy intervention did not affect reproductive parameters but did affect pregnancy outcomes including litter size. Male Obese-OFS offspring had significantly lower percent body fat than Obese-HFS at 17 weeks. Female Obese-S and Obese-OFS offspring had significantly lower fasting glucose at 17 weeks compared with Obese-Control and Obese-HFS. Clostridium cluster XI was higher in Obese-HFS and Obese-S dams at birth compared with all other groups. Dams with an adverse pregnancy outcome had significantly lower (p = 0.035 Lactobacillus spp. compared with dams with normal or small litters. At weaning, male offspring

  6. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

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    Li, Jing [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology & Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-NancyUniversité, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

  7. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

    International Nuclear Information System (INIS)

    Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

  8. 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

  9. 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.

  10. 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.

  11. Prenatal ethanol enhances rotational behavior to apomorphine in the 24-month-old rat offspring with small striatal lesion.

    Science.gov (United States)

    Gomide, Vânia C; Chadi, Gerson

    2004-01-01

    Pregnant Wistar rats received a hyperproteic liquid diet containing 37.5% ethanol-derived calories during gestation. Isocaloric amount of liquid diet, with maltose-dextrin substituted for ethanol, was given to control pair-fed dams. Offsprings were allowed to survive until 24 months of age. A set of aged female offsprings of both control diet and ethanol diet groups was registered for spontaneous motor activity, by means of an infrared motion sensor activity monitor, or for apomorphine-induced rotational behavior, while another lot of male offsprings was submitted to an unilateral striatal small mechanical lesion by a needle, 6 days before rotational recordings. Prenatal ethanol did not alter spontaneous motor parameters like resting time as well as the events of small and large movements in the aged offsprings. Bilateral circling behavior was already increased 5 min after apomorphine in the unlesioned offsprings of both the control and ethanol diet groups. However, it lasted more elevated for 45- to 75-min time intervals in the gestational ethanol-exposed offsprings, while decreasing faster in the control offsprings. Apomorphine triggered a strong and sustained elevation of contraversive turns in the striatal-lesioned 24-month-old offsprings of the ethanol group, but only a small and transient elevation was seen in the offsprings of the control diet group. Astroglial and microglial reactions were seen surrounding the striatal needle track lesion. Microdensitometric image analysis demonstrated no differences in the levels of tyrosine hydroxylase immunoreactivity in the striatum of 24-month-old unlesioned and lesioned offsprings of control and alcohol diet groups. The results suggest that ethanol exposure during gestation may alter the sensitivity of dopamine receptor in aged offsprings, which is augmented by even a small striatal lesion.

  12. Expression of neuropeptide Y and pro-opiomelanocortin in hypothalamic arcuate nucleus in 17α-ethinyl estradiol-induced intrahepatic cholestasis pregnant rat offspring.

    Science.gov (United States)

    Shi, Qingyun; Wang, Jingjing; Yan, Shi; Zhao, Jin; Li, Hongxia

    2014-02-01

    The purpose of this study was to investigate the expression of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the hypothalamic arcuate nucleus of intrahepatic cholestasis pregnant (ICP) offspring. The model of ICP rats was established by injecting s.c. 17α-ethinyl estradiol. The expression of NPY and POMC in female offspring was determined by quantitative real-time reverse transcription polymerase chain reaction, western blotting and immunohistochemistry at birthday and 6 months. ICP group offspring had lower bodyweight at birthday. ICP offspring were markedly heavier than control offspring after 6 months. mRNA and protein expression of NPY and POMC significantly increased at 6 months as compared with the birthday among control offspring. Among ICP offspring, mRNA and protein expression of NPY and POMC also were higher at 6 months than at birthday. The mRNA and protein expression of NPY were higher in ICP offspring than that of control offspring at birthday. The mRNA and protein expression of POMC were decreased in ICP offspring than that of control offspring. After 6 months, the mRNA expression and protein expression of NPY also were higher in ICP offspring than that of control offspring. The mRNA expression and protein expression of POMC also were decreased in ICP offspring than that of control offspring. The results were confirmed by immunohistochemistry. ICP offspring demonstrated evidence of persistent appetite stimulation with significantly upregulated NPY expression and reduced POMC expression at birthday and 6 months. ICP offspring showed a hunger state and then gained weight. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  13. 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.

  14. A Calcium-Deficient Diet in Rat Dams during Gestation Decreases HOMA-β% in 3 Generations of Offspring.

    Science.gov (United States)

    Takaya, Junji; Yamanouchi, Sohsaku; Tanabe, Yuko; Kaneko, Kazunari

    2016-01-01

    Prenatal malnutrition can affect the phenotype of offspring by altering epigenetic regulation. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. We hypothesized that a Ca-deficient diet during pregnancy would alter insulin resistance and secretion in more than 1 generation of offspring. Female Wistar rats consumed either a Ca-deficient or a control diet ad libitum from 3 weeks before conception to 21 days after parturition and were mated with control males. Randomly selected F1 and F2 females were mated with males of each generation on postnatal day 70. The F1 and F2 dams were fed a control diet ad libitum during pregnancy and lactation. All offspring were fed a control diet starting at the time of weaning and were sacrificed on day 180. HOMA-β% decreased in F1 through F3, and levels in F2 and F3 males and females were significantly lower than in controls. The mean levels of insulin and HOMA-IR were higher in F1 males but lower in F3 males than in control males. The HOMA-IR did not differ between any of the female offspring and controls. Maternal Ca restriction during pregnancy and/or lactation influences insulin secretion in 3 generations of offspring. © 2017 S. Karger AG, Basel.

  15. Mother knows best: dominant females determine offspring dispersal in red foxes (Vulpes vulpes.

    Directory of Open Access Journals (Sweden)

    Helen M Whiteside

    Full Text Available Relatedness between group members is central to understanding the causes of animal dispersal. In many group-living mammals this can be complicated as extra-pair copulations result in offspring having varying levels of relatedness to the dominant animals, leading to a potential conflict between male and female dominants over offspring dispersal strategies. To avoid resource competition and inbreeding, dominant males might be expected to evict unrelated males and related females, whereas the reverse strategy would be expected for dominant females.We used microsatellites and long-term data from an urban fox (Vulpes vulpes population to compare dispersal strategies between offspring with intra- and extra-group fathers and mothers of differing social status in red foxes. Relatedness to the dominant male had no effect on dispersal in offspring of either sex, whereas there was a strong effect of relatedness to resident females on offspring dispersal independent of population density. Males with dominant mothers dispersed significantly more often than males with subordinate mothers, whereas dispersing females were significantly more likely to have subordinate mothers compared to philopatric females.This is the first study to demonstrate that relatedness to resident females is important in juvenile dispersal in group-living mammals. Male dispersal may be driven by inbreeding avoidance, whereas female dispersal appears to be influenced by the fitness advantages associated with residing with the same-sex dominant parent. Selection pressure for paternal influence on offspring dispersal is low due to the limited costs associated with retaining unrelated males and the need for alternative inbreeding avoidance mechanisms between the dominant male and his female offspring. These findings have important implications for the evolution of dispersal and group living in social mammals, and our understanding of a key biological process.

  16. Mother knows best: dominant females determine offspring dispersal in red foxes (Vulpes vulpes).

    Science.gov (United States)

    Whiteside, Helen M; Dawson, Deborah A; Soulsbury, Carl D; Harris, Stephen

    2011-01-01

    Relatedness between group members is central to understanding the causes of animal dispersal. In many group-living mammals this can be complicated as extra-pair copulations result in offspring having varying levels of relatedness to the dominant animals, leading to a potential conflict between male and female dominants over offspring dispersal strategies. To avoid resource competition and inbreeding, dominant males might be expected to evict unrelated males and related females, whereas the reverse strategy would be expected for dominant females. We used microsatellites and long-term data from an urban fox (Vulpes vulpes) population to compare dispersal strategies between offspring with intra- and extra-group fathers and mothers of differing social status in red foxes. Relatedness to the dominant male had no effect on dispersal in offspring of either sex, whereas there was a strong effect of relatedness to resident females on offspring dispersal independent of population density. Males with dominant mothers dispersed significantly more often than males with subordinate mothers, whereas dispersing females were significantly more likely to have subordinate mothers compared to philopatric females. This is the first study to demonstrate that relatedness to resident females is important in juvenile dispersal in group-living mammals. Male dispersal may be driven by inbreeding avoidance, whereas female dispersal appears to be influenced by the fitness advantages associated with residing with the same-sex dominant parent. Selection pressure for paternal influence on offspring dispersal is low due to the limited costs associated with retaining unrelated males and the need for alternative inbreeding avoidance mechanisms between the dominant male and his female offspring. These findings have important implications for the evolution of dispersal and group living in social mammals, and our understanding of a key biological process.

  17. 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

  18. Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females

    Science.gov (United States)

    Bayol, S A; Simbi, B H; Bertrand, J A; Stickland, N C

    2008-01-01

    We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-γ (PPARγ), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity. PMID:18467362

  19. Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females.

    Science.gov (United States)

    Bayol, S A; Simbi, B H; Bertrand, J A; Stickland, N C

    2008-07-01

    We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-gamma (PPARgamma), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity.

  20. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    Directory of Open Access Journals (Sweden)

    Chen HH

    2015-03-01

    Full Text Available Hwei-Hsien Chen,1,2,* Yao-Chang Chiang,3,4,* Zung Fan Yuan,5,6 Chung-Chih Kuo,5,6 Mei-Dan Lai,2 Tsai-Wei Hung,1 Ing-kang Ho,1,3,4 Shao-Tsu Chen2,7 1Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan; 2Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan; 3Center for Drug Abuse and Addiction, China Medical University Hospital, 4Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 5Master Program in Physiological and Anatomical Medicine, 6Department of Physiology, School of Medicine, Tzu Chi University, 7Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan *These authors contributed equally to this work Abstract: Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female

  1. Effect of parental morphine addiction on extracellular glutamate concentration of dentate gyrus in rat offsprings

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    rahele Assaee

    2004-01-01

    Findings: In male offsprings of sham control1, sham control2, test1 and test2 basal and electrical stimulated of extracellular glutamate concentration of dentate gyrus were: 0.67±0.04, 1.11±0.1, and in female offsprings were 0.47±0.06, 0.88±0.05 (n=5. The basal and stimulated extra cellular glutamate concentration of dentate gyrus was decreased in both test1 and test2 offsprings. It was less in test1 than test2 offsprings. The glutamate concentration of dentate gyrus in female offsprings of test1 group was less than that of the male offsprings. conclusion: The results suggest that parental morphine addiction may cause learning deficiency through reduction of extracellular glutamate concentration in dentate gyrus so the side effects of parental morphine addiction in offsprings must be considered.

  2. Effects of environmental enrichment during abstinence in morphine dependent parents on anxiety, depressive-like behaviors and voluntary morphine consumption in rat offspring.

    Science.gov (United States)

    Pooriamehr, Alireza; Sabahi, Parviz; Miladi-Gorji, Hossein

    2017-08-24

    Chronic morphine exposure during puberty increased morphine-induced rewarding effects and sensitization in the next generation. Given the well-known beneficial effects of environmental enrichment on the severity of physical and psychological dependence on morphine, we examined effects of enriched environment during morphine abstinence in morphine dependent parental rats before mating on the anxiety and depressive-like behaviors, and voluntary morphine consumption in their offspring. Paternal and/or maternal rats were injected with bi-daily doses (10mg/kg, 12h intervals) of morphine for 14days followed by rearing in a standard environment (SE) or enriched environment (EE) during 30days of morphine abstinence before mating. The pubertal male and female rat offspring were tested for anxiety (the elevated plus maze- EPM) and depression (sucrose preference test-SPT), and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that EE experience in morphine-dependent both parents result in an increase in the percentage of time spent into open arms/time spent on both arms using EPM in male offspring, higher levels of sucrose preference in female offspring and lower levels of voluntary morphine consumption in male and female offspring. Thus, EE experience in morphine-dependent both parents reduced anxiety, depressive-like behavior and also the voluntary morphine consumption in their offspring during puberty which may prevent the vulnerability of the next generation to drug abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Insulin sensitivity is normalized in the third generation (F3 offspring of developmentally programmed insulin resistant (F2 rats fed an energy-restricted diet

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    Martin John F

    2008-10-01

    Full Text Available Abstract Background/Aims The offspring and grandoffspring of female rats fed low protein diets during pregnancy and lactation, but fed nutritionally adequate diets thereafter, have been shown to exhibit altered insulin sensitivity in adulthood. The current study investigates the insulin sensitivity of the offspring and grandoffspring of female rats fed low protein diets during pregnancy, and then maintained on energy-restricted diets post weaning over three generations. Methods Female Sprague Dawley rats (F0 were mated with control males and protein malnourished during pregnancy/lactation. F1 offspring were then weaned to adequate but energy-restricted diets into adulthood. F1 dams were fed energy-restricted diets throughout pregnancy/lactation. F2 offspring were also fed energy-restricted diets post weaning. F2 pregnant dams were maintained as described above. Their F3 offspring were split into two groups; one was maintained on the energy-restricted diet, the other was maintained on an adequate diet consumed ad libitum post weaning. Results F2 animals fed energy-restricted diets were insulin resistant (p ad libitum postweaning diets (p Conclusion Maternal energy-restriction did not consistently program reduced insulin sensitivity in offspring over three consecutive generations. The reasons for this remain unclear. It is possible that the intergenerational transmission of developmentally programmed insulin resistance is determined in part by the relative insulin sensitivity of the mother during pregnancy/lactation.

  4. 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.

  5. Resveratrol Intake During Pregnancy and Lactation Modulates the Early Metabolic Effects of Maternal Nutrition Differently in Male and Female Offspring.

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    Ros, Purificación; Díaz, Francisca; Freire-Regatillo, Alejandra; Argente-Arizón, Pilar; Barrios, Vicente; Argente, Jesús; Chowen, Julie A

    2018-02-01

    Poor maternal nutrition can have detrimental long-term consequences on energy homeostasis in the offspring. Resveratrol exerts antioxidant and antiobesity actions, but its impact during development remains largely unknown. We hypothesized that resveratrol intake during pregnancy and lactation could improve the effects of poor maternal nutrition on offspring metabolism. Wistar rats received a low-fat diet (LFD; 10.2% kcal from fat) or high-fat diet (HFD; 61.6% kcal from fat), with half of each group receiving resveratrol in their drinking water (50 mg/L) during pregnancy and lactation. Body weight (BW) of dams was measured at treatment onset and weaning [postnatal day (PND) 21] and of pups at birth and PND21, at which time dams and pups were euthanized. Although HFD dams consumed more energy, their BW at the end of lactation was unaffected. Mean litter size was not modified by maternal diet or resveratrol. At birth, male offspring from HFD and resveratrol (HFD + R) dams weighed less than those from LFD and resveratrol (LFD + R) dams. On PND21, pups of both sexes from HFD dams weighed more, had more visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT), and had higher serum leptin levels than those from LFD dams. Resveratrol reduced BW, leptin, VAT, and SCAT, with females being more affected, but increased glycemia. Neuropeptide levels were unaffected by resveratrol. In conclusion, resveratrol intake during pregnancy and lactation decreased BW and adipose tissue content in offspring of dams on an HFD but did not affect offspring from LFD-fed dams, suggesting that the potential protective effects of resveratrol during gestation/lactation are diet dependent. Copyright © 2018 Endocrine Society.

  6. Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

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    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.

  7. Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring.

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    El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H

    2010-06-10

    Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in

  8. Exposure of pregnant rats to uranium and restraint stress: Effects on postnatal development and behavior of the offspring

    International Nuclear Information System (INIS)

    Sanchez, Domenec J.; Belles, Montserrat; Albina, Maria L.; Gomez, Mercedes; Linares, Victoria; Domingo, Jose L.

    2006-01-01

    The effects on postnatal development and behavior were assessed in the offspring of female rats concurrently exposed to uranium (U) and restraint stress. Adult female rats were administered uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 40 and 80 mg/(kg day) for 4 weeks before mating with untreated males, as well as during pregnancy and lactation. One-half of female rats in each group were concurrently subjected to restraint (2 h/day). On gestation day 14, one-half of restrained and unrestrained rats were sacrificed in order to evaluate maternal toxicity and gestational parameters. Pups were evaluated for physical development, neuromotor maturation, and behavior. Uranium concentrations were also determined in various tissues of dams and fetuses. In all uranium-treated groups, the highest concentrations of this element were found in kidney and bone, being considerably higher than those in brain. Uranium levels in tissues of dam or fetuses were not significantly affected by restraint. No significant interactions between uranium and restraint could be observed in maternal toxicity. Moreover, no relevant effects of uranium, maternal restraint, or their combination were noted on developmental landmarks in the offspring. In the passive avoidance test, at 40 and 80 mg UAD/(kg day) restraint significantly modified passive avoidance acquisition (T1) and retention time (T2) 24 h later. However, no significant differences were observed on the Morris water maze test. The results of the present study indicate that, in general terms, exposure of female rats to UAD before mating with untreated males, as well as during gestation and lactation, did not cause relevant dose-related adverse effects on postnatal development and behavior of the offspring. The influence of stress was very limited

  9. A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

    Science.gov (United States)

    Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

    2010-04-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

  10. A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

    Science.gov (United States)

    Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

    2010-01-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

  11. Maternal exposure to environmental enrichment before and during gestation influences behaviour of rat offspring in a sex-specific manner.

    Science.gov (United States)

    Zuena, Anna Rita; Zinni, Manuela; Giuli, Chiara; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giuliani, Alessandro; Catalani, Assia; Casolini, Paola; Cozzolino, Roberto

    2016-09-01

    The beneficial effects of Environmental Enrichment (EE) applied immediately after weaning or even in adulthood have been widely demonstrated. Less is known about the possible changes in behaviour and brain development of the progeny following the exposure of dams to EE. In order to further investigate this matter, female rats were reared in EE for 12weeks, from weaning until delivery. After having confirmed the presence of relevant behavioural effects of EE, both control and EE females underwent mating. Maternal behaviour was observed and male and female offspring were then administered a battery of behavioural test at different ages. EE mothers showed a decreased frequency of total nursing and, during the first 2days of lactation, an increase in licking/grooming behaviour. Maternal exposure to EE affected offspring behaviour in a sex-specific manner: social play behaviour and anxiety-like behaviour were increased in males but not in females and learning ability was improved only in females. As a general trend, maternal EE had a marked influence on motility in male and female offspring in both locomotor activity and swimming speed. Overall, this study highlights the importance of environmental stimulation, not only in the animals directly experiencing EE, but for their progeny too, opening the way to new hypothesis on the heritability mechanisms of behavioural traits. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Developmental Effects of Prenatal Exposure to Bisphenol A on the Uterus of Rat Offspring

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    Gilbert Schönfelder

    2004-09-01

    Full Text Available Exposure to estrogenic compounds during critical periods of fetal development could result in adverse effects on the development of reproductive organs that are not apparent until later in life. Bisphenol A (BPA, which is employed in the manufacture of a wide range of consumer products, is a prime candidate for endocrine disruption. We examined BPA to address the question of whether in utero exposure affects the uterus of the offspring and studied the expression and distribution of the estrogen receptors alpha (ERβ and beta (ERα, because estrogens influence the development, growth, and function of the uterus through both receptors. Gravid Sprague-Dawley dams were administered by gavage either 0.1 or 50 mg/kg per day BPA or 0.2 mg/kg per day 17α-ethinyl estradiol (EE2 as reference dose on gestation days 6 through 21. Female offspring were killed in estrus. Uterine morphologic changes as well as ERα and ERβ distribution and expression were measured by immunohistochemistry and Western blot analysis. Striking morphologic changes were observed in the uterine epithelium of postpubertal offspring during estrus of the in utero BPA-treated animals (the thickness of the total epithelium was significantly reduced. ERβ expression was increased in the 50-mg BPA and EE2-treated group. In contrast, we observed significantly decreased ERβ expression in all BPA- and EE2-treated animals when compared with the control. In summary, these results clearly indicate that in utero exposure of rats to BPA promotes uterine disruption in offspring. We hypothesize that the uterine disruption could possibly be provoked by a dysregulation of ERα and ERβ.

  13. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring.

    Science.gov (United States)

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    The mother's consumption of high-fat food can affect glucose metabolism and the hypothalamic-pituitary-adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Female rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers' diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels. According to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group. Mothers' high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

  14. Reproductive ability of pubertal male and female rats

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    T. Zemunik

    2003-07-01

    Full Text Available Ten Fisher rats 50 to 55 days of age made up the pubertal group, and ten rats 90 to 95 days of age served as the controls. The testicular and epididymal weights and volumes of the pubertal males were lower than those of the controls (P0.05. At the beginning of gestation, the pubertal dams weighed less than the controls (P<0.001 but following uterectomy the body weights were equal. Pubertal dams delivered fewer pups than the controls (8.1 ± 2.5 vs 10.4 ± 1.3, P<0.05. There was no difference in the body weights of their offspring or in the weights of their placentas. The results suggest that, in contrast to their female counterparts, pubertal male rats are not fully mature and have not reached complete reproductive capacity at 50-55 days of age.

  15. The female advantage in natural populations of gynodioecious Plantago coronopus: seed quantity vs. offspring quality.

    Science.gov (United States)

    van der Meer, Sascha; Sebrechts, Thomas; Vanderstraeten, Sylvette; Jacquemyn, Hans

    2017-12-01

    In gynodioecious plant species, females can only persist when they have a reproductive advantage in comparison with hermaphrodites. However, several studies have shown that females do not necessarily produce more seeds than hermaphrodites, since seed production can be affected by population characteristics, such as female frequency or population size. The aim of this study was to quantify the female advantage across a large number of natural populations, examine its relationship with population sex ratio and size, and to assess the role of competition on the magnitude of the female advantage. We sampled 27 populations of Plantago coronopus (nuclear-cytoplasmic gynodioecy) along the Belgian and Dutch coast. In each population, we estimated population sex ratio and size, and assessed seed production per flower and seed production per plant. Subsequently, germination, growth, and competition experiments were performed in the greenhouse to determine the female advantage regarding offspring quality. Females produced fewer seeds per plant than hermaphrodites (FA = 0.90), and seed production was negatively related to female frequency. Since both sex morphs were equally affected by pollen availability, the female advantage was not related to population sex ratio. On the other hand, offspring of females showed higher germination and growth rates, resulting in higher competitive abilities when seeds of a female and a hermaphrodite were grown together. Overall, these results indicate that differences in competitive abilities between the offspring of females and hermaphrodites may have contributed to the maintenance of females in relatively high frequencies in populations of this short-lived gynodioecious plant species.

  16. Steroid Hormones and Female Energy Balance: Relation to Offspring Primary Sex Ratio

    NARCIS (Netherlands)

    Aslam, M.L.; Woelders, H.

    2017-01-01

    Birds can manipulate the offspring sex ratio under natural and experimental conditions. Various factors related to the avian mother, as well as her eggs, have been reported to be linked with the sex determination process. These factors appear to affect the chance of laying a male or female egg

  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. In Utero Phthalate Effects in the Female Rat: A Model for MRKH Syndrome

    Science.gov (United States)

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly define etiology. Reproductive toxicity of phthlate esters (PEs) occurs in rat offspring exposed in utero. a phenome...

  19. In utero phthalate effects in the female rat: a model for MRKH syndrome##

    Science.gov (United States)

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phen...

  20. Effects of Maternal Lead Acetate Exposure during Lactation on Postnatal Development of Testis in Offspring Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mehran Dorostghoal

    2011-03-01

    Full Text Available Objective(sDuring recent years, there has been an increasing interest in contribution of environmental pollutants as heavy metals to human male infertility. Present study was aimed to investigate the effects of maternal lead acetate exposure during lactation on postnatal development of testis in offspring rats.Materials and MethodsA total of 60 female rats randomly divided into four equal groups; control and three treatment groups received 20, 100 and 300 mg/kg/day lead acetate via drinking water from day 2 to day 21 of lactation. At 7, 14, 21, 28, 60, 90 and 120 days after birth, the testis weight and volume of offspring were measured and their epididymal semen analyzed. Following tissue processing, 5 μm sections were stained with haematoxylin-eosin and evaluated with quantitative techniques. Testicular parameters in different groups were compared by one-way ANOVA.ResultsTestis weight and volume of offspring decreased significantly in a dose-related manner in moderate (P< 0.05 and high (P< 0.01 doses groups. Dose-dependent significant reductions were seen in seminiferous tubules diameter and germinal epithelium height during neonatal, prepubertal and postpubertal periods in moderate (P< 0.05 and high (P< 0.01 doses groups until 90 and 120 days after birth, respectively. Significant decreases were observed in mean sperm density of offspring at puberty in moderate and high doses groups until 90 and 120 days after birth, respectively. Testosterone levels decreased significantly in a dose-related manner at puberty in moderate and high doses groups. ConclusionPresent study showed maternal lead acetate exposure during lactation caused dose-related and long-term alterations of testicular parameters in offspring rats.

  1. 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.

  2. 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.

  3. Selection on female behaviour fluctuates with offspring environment.

    Science.gov (United States)

    Taylor, R W; Boutin, S; Humphries, M M; McAdam, A G

    2014-11-01

    Temporal variation in selection has long been proposed as a mechanism by which genetic variation could be maintained despite short-term strong directional selection and has been invoked to explain the maintenance of consistent individual differences in behaviour. We tested the hypothesis that ecological changes through time lead to fluctuating selection, which could promote the maintenance of variation in female behavioural traits in a wild population of North American red squirrels. As predicted, linear selection gradients on female aggression and activity significantly fluctuated across years depending on the level of competition among juveniles for vacant territories. This selection acted primarily through juvenile overwinter survival rather than maternal fecundity. Incorporating uncertainty in individual measures of behaviour reduced the magnitude of annual selection gradients and increased uncertainty in these estimates, but did not affect the overall pattern of temporal fluctuations in natural selection that coincided with the intensity of competition for vacant territories. These temporal fluctuations in selection might, therefore, promote the maintenance of heritable individual differences in behaviour in this wild red squirrel population. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  4. 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

  5. Attenuation by dextromethorphan on the higher liability to morphine-induced reward, caused by prenatal exposure of morphine in rat offspring

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    Tao Pao-Luh

    2009-11-01

    Full Text Available Abstract Co-administration of dextromethorphan (DM with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p. in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers.

  6. 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.

  7. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring.

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    Ana Paula García

    Full Text Available Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively were analyzed in male and female offspring of control and 20% caloric-restricted (from 1-12 d of pregnancy (CR dams. Body weight (BW, the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH(+ and NPY(+, suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH(+ and NPY(+. Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture.

  8. The effects of co-administration of opium and morphine with nicotine during pregnancy on spatial learning and memory of adult male offspring rats.

    Science.gov (United States)

    Sepehri, Gholamreza; Parsania, Shahrnaz; Hajzadeh, Mousa-Al-Reza; Haghpanah, Tahereh; Sheibani, Vahid; Divsalar, Kouros; Shekarforoush, Shahnaz; Afarinesh, Mohammad Reza

    2014-09-01

    Smoking opium/cigarette is a global health concern. The aim of this study was to examine learning and memory of rat male offsprings whose mothers had been exposed to either opium or morphine with nicotine during pregnancy. Wistar rats were used for the experiments. In the female rats, opium, morphine and nicotine dependencies were induced by daily injections of drug solution for 10 days before mating. Spatial memory was tested by Morris water maze test in male pups at the postnatal day 60. The duration that took until the rats found the platform in the maze and also their swimming speed were recorded. An increase in the platform finding duration was observed for the pups of dependent mothers in comparison with the control in the training trial (Popium/morphine and nicotine significantly decreased the time spent in the trigger zone to find the hidden platform (Peffect on the swimming speed in the probe test. However, no significant difference was observed in the learning and memory behavior of offspring whose mothers received morphine, opium, nicotine or the co-administration of either morphine or opium with nicotine. The present study showed that the opium, morphine and nicotine abuse and co-administration of opium/morphine with nicotine during pregnancy may cause deficits in spatial learning of male rat offspring. Based on our data, no synergistic effects of co-drug administration were observed on learning and memory in male rat offspring.

  9. Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice.

    Science.gov (United States)

    Maruoka, Takashi; Kodomari, Ikuko; Yamauchi, Rena; Wada, Etsuko; Wada, Keiji

    2009-04-17

    The maternal environment is thought to be important for fetal brain development. However, the effects of maternal environment are not fully understood. Here, we investigated whether enrichment of the maternal environment can influence prenatal brain development and postnatal behaviors in mice. An enriched environment is a housing condition with several objects such as a running wheel, tube and ladder, which are thought to increase sensory, cognitive and motor stimulation in rodents compared with standard housing conditions. First, we measured the number of BrdU-positive cells in the hippocampal dentate gyrus of fetuses from pregnant dams housed in an enriched environment. Our results revealed that maternal enrichment influences cell proliferation in the hippocampus of female, but not male, fetuses. Second, we used the open-field test to investigate postnatal behaviors in the offspring of dams housed in the enriched environment during pregnancy. We found that maternal enrichment significantly affects the locomotor activity and time spent in the center of the open-field in female, but not male, offspring. These results indicate that maternal enrichment influences prenatal brain development and postnatal behaviors in female offspring.

  10. Propofol Exposure in Pregnant Rats Induces Neurotoxicity and Persistent Learning Deficit in the Offspring

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    Ming Xiong

    2014-05-01

    Full Text Available Propofol is a general anesthetic widely used in surgical procedures, including those in pregnant women. Preclinical studies suggest that propofol may cause neuronal injury to the offspring of primates if it is administered during pregnancy. However, it is unknown whether those neuronal changes would lead to long-term behavioral deficits in the offspring. In this study, propofol (0.4 mg/kg/min, IV, 2 h, saline, or intralipid solution was administered to pregnant rats on gestational day 18. We detected increased levels of cleaved caspase-3 in fetal brain at 6 h after propofol exposure. The neuronal density of the hippocampus of offspring was reduced significantly on postnatal day 10 (P10 and P28. Synaptophysin levels were also significantly reduced on P28. Furthermore, exploratory and learning behaviors of offspring rats (started at P28 were assessed in open-field trial and eight-arm radial maze. The offspring from propofol-treated dams showed significantly less exploratory activity in the open-field test and less spatial learning in the eight-arm radial maze. Thus, this study suggested that propofol exposure during pregnancy in rat increased cleaved caspsase-3 levels in fetal brain, deletion of neurons, reduced synaptophysin levels in the hippocampal region, and persistent learning deficits in the offspring.

  11. 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

  12. Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway

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    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.

  13. Biochemical parameters of pregnant rats and their offspring exposed to different doses of inorganic mercury in drinking water.

    Science.gov (United States)

    Oliveira, Cláudia S; Oliveira, Vitor A; Ineu, Rafael P; Moraes-Silva, Lucélia; Pereira, Maria E

    2012-07-01

    This work investigated the effects of low and high doses of inorganic mercury in drinking water on biochemical parameters of pregnant rats and their offspring. Female Wistar rats were treated during pregnancy with 0, 0.2, 0.5, 10 or 50 μg Hg(2+)/mL as HgCl(2). Rats were euthanized on day 20 of pregnancy. Pregnant rats presented a decrease in total water intake in all doses of mercury tested. At high doses, a decrease in the total food intake and in body weight gain was observed. Pregnant rats exposed to 50 μg Hg(2+)/mL presented an increase in kidney relative weight. Mercury exposure did not change serum urea and creatinine levels in any of the doses tested. Moreover, mercury exposure did not change porphobilinogen synthase activity of kidney, liver and placenta from pregnant rats in any of the doses tested, whereas fetuses of pregnant rats exposed to 50 μg Hg(2+)/mL presented an increase in the hepatic porphobilinogen synthase activity. In general, pregnant rats presented alterations due to HgCl(2) exposure in drinking water. However, only the dose 50 μg Hg(2+)/mL appeared to be enough to cross the blood-placenta barrier, since at this dose the fetuses presented change in the porphobilinogen synthase activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

    Science.gov (United States)

    Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

    2017-05-01

    Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

  16. Prenatal androgen excess programs metabolic derangements in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Dai, Xiaonan; Wang, Jing; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2013-04-01

    Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5α-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5-8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30- and 60-min glucose levels than the controls after insulin stimulation during 5-8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development.

  17. 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.

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

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    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.

  19. Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

    Science.gov (United States)

    Murray, Brendan G; Davies, Don A; Molder, Joel J; Howland, John G

    2017-05-01

    Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

    Science.gov (United States)

    Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

    2016-10-17

    Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Prenatal Stress Produces Sex Specific Changes in Depression-like Behavior in Rats: Implications for Increased Vulnerability in Females

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Arentzen, Tine S; Dyrby, Tim

    2015-01-01

    Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression...... and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute...... affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects...

  2. Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats.

    Science.gov (United States)

    Mendes Garrido Abregú, Facundo; Gobetto, María Natalia; Juriol, Lorena Vanesa; Caniffi, Carolina; Elesgaray, Rosana; Tomat, Analía Lorena; Arranz, Cristina

    2018-06-01

    Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Peculiarities of oxidative modification of proteins indices in blood plasma of the female rats’ offspring with experimental gestational diabetes depending on sex, age and basal glycemia level

    Directory of Open Access Journals (Sweden)

    O. V. Gancheva

    2015-04-01

    Full Text Available Analysis of products of oxidative modification of proteins (OMP in correlation with plasma catalase activity will help us to define the state of oxidative stress parameters in the normal animals and in the female rats’ offspring with experimental gestational diabetes (EGD. Itwilldefine their role in organism’s reorganization aimed to activation of compensatory and defensive mechanisms both at the cellular level and at the level of homeostasis. We’ll also define its alteration in animals with the prenatal negative influence of chronic hyperglycemia. The aim of research wasto study peculiarities of OMP parameters and plasma catalase activity of the female rats’offspring with EGD in dependence on sex, age and basal glycemia level. Materials and methods.The research was carried out on 80 rats (males and females offspring of the female rats with normal pregnancy and 80 offspring (males and females of the female rats with EGD. The animals were grouped by the age 2, 4, 6 and 18 months; 20 animals in each group. Animals were freely allowed to standard food and water. When animals reached appropriate age they were decapitated under thiopental anesthesia (40 mg/kg. Glucose was measured by glucose oxidative method in all groups of animals. In order to define the intensity of oxidative reactions in blood plasma of laboratory animals the degree of OMP by Halliwell method was done. Wemeasuredlevelofaldehydephenylhydrazone (APH which is thought to be as early mark of proteins oxidation, and ketonephenylhydrazone (KPH which is referred to late mark of protein destruction. The state of antioxidative system was evaluated by plasma catalase activity with the help of spectrophotometric method. The obtained data was processed by statistic programs VIDAS-2.5 (Kontron Elektronik, Германия, EXCEL MS Office 2007 (Microsoft Corp., США, STATISTICA 6.0 (Stat-Soft, 2001. Results and discussion. In the present research, we have observed the decrease of

  4. 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).

  5. Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring

    Directory of Open Access Journals (Sweden)

    Lourdes Rodríguez

    2015-01-01

    Full Text Available Objective. Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10% wt/vol throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny.

  6. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    Science.gov (United States)

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  7. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Science.gov (United States)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

  8. The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood

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    Guilherme D’Aprile Marchesi

    Full Text Available OBJECTIVE: To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs from birth until adulthood. METHODS: Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. RESULTS: The level of food consumption was lower in male offspring (IVC=171.7±9; CC=193.1±20 than in female offspring (IVC=100.6±7; CC=123.4±0.4, whereas the water intake was higher in female offspring (IVC=149.8±11; CC=99.2±0 than in male offspring (IVC=302.5±25; CC=249.7±22 at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9±0.5; CCs=22.95±0.3 and female (IVCs=26.2±0.3; CCs=23.1±0.3 offspring. The respiratory resistance (IVC=68.8±2.8; CC=50.6±3.0 and elastance (IVC=42.0±3.9; CC=32.4±2.0 at 300 µm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4±0.2; CC=15±0.4 and female (IVC=13.5±0.4; CC=15.9±0.6 offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5±9.7; CC=285.0±22.8, neutrophil (IVC=13.1±4.8; CC=75.6±4.1 and macrophage (IVC=95.2±11.8; CC=170.0±18.8 counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. CONCLUSIONS: The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages.

  9. The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood

    Science.gov (United States)

    Marchesi, Guilherme D’Aprile; de Fatima Soto, Sônia; de Castro, Isac; Rodrigues, Thiago Guimarães; Moriya, Henrique Takachi; de Almeida, Francine Maria; Pazetti, Rogerio; Heimann, Joel Claudio; Furukawa, Luzia Naôko Shinohara

    2017-01-01

    OBJECTIVE: To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs) from birth until adulthood. METHODS: Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs) and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. RESULTS: The level of food consumption was lower in male offspring (IVC=171.7±9; CC=193.1±20) than in female offspring (IVC=100.6±7; CC=123.4±0.4), whereas the water intake was higher in female offspring (IVC=149.8±11; CC=99.2±0) than in male offspring (IVC=302.5±25; CC=249.7±22) at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9±0.5; CCs=22.95±0.3) and female (IVCs=26.2±0.3; CCs=23.1±0.3) offspring. The respiratory resistance (IVC=68.8±2.8; CC=50.6±3.0) and elastance (IVC=42.0±3.9; CC=32.4±2.0) at 300 µm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4±0.2; CC=15±0.4) and female (IVC=13.5±0.4; CC=15.9±0.6) offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5±9.7; CC=285.0±22.8), neutrophil (IVC=13.1±4.8; CC=75.6±4.1) and macrophage (IVC=95.2±11.8; CC=170.0±18.8) counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. CONCLUSIONS: The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages. PMID:28355363

  10. Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring

    DEFF Research Database (Denmark)

    Lykkedegn, Sine; Sorensen, Grith Lykke; Beck-Nielsen, Signe Sparre

    2016-01-01

    Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung...... surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL) or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OH)D) determinations. After cesarean section at gestational day 19 (E19) or day 22 (E22), placental weight, birth weight, crown......-rump-length (CRL), oxygenation (SaO2) at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR). S-25(OH)D was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p

  11. Premature reproductive aging in female rats after developmental exposure to mixtures of endocrine disrupters

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Petersen, Marta Axelstad; Christiansen, Sofie

    2013-01-01

    of 13 estrogenic and anti-androgenic chemicals, including phthalates, pesticides, UV-filters, bisphenol A, butylparaben and paracetamol, and the mixture ratio was chosen to reflect high-end human intakes. Groups received combined exposures of 0,100, 150, 200 or 450 times high-end human intake levels......Long-lasting and delayed reproductive effects of developmental exposure to mixtures of environmental chemicals were investigated in female rats. Wistar rats were dosed during gestation and lactation to mixtures of endocrine disrupters, and effects in offspring were studied. The mixtures consisted....... Additionally, groups received mixtures including only the anti-androgens or estrogens at 200 or 450 times human intake. Female offspring exposed to the high dose mixture of all 13 chemicals showed earlier reproductive aging measured as early onset of irregular estrous cycle as compared to controls...

  12. 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.

  13. Maternal sodium butyrate supplement elevates the lipolysis in adipose tissue and leads to lipid accumulation in offspring liver of weaning-age rats.

    Science.gov (United States)

    Zhou, Jiabin; Gao, Shixing; Chen, Jinglong; Zhao, Ruqian; Yang, Xiaojing

    2016-07-22

    Sodium butyrate (SB) is reported to regulate lipid metabolism in mammals, and the relationship between maternal nutrition and offspring growth has drawn much attention in the last several years. To elucidate the effects of maternal dietary SB supplementation on hepatic lipid metabolism in weaning rats, we fed 16 primiparous purebred female SD rats either a chow-diet or a 1 % sodium butyrate diet throughout pregnancy and lactation. At weaning age, samples of the maternal subcutaneous adipose tissue and offspring liver were taken. The serum indexes and expressions of proteins related to lipid metabolism were detected in the mother and offspring, respectively. The results showed that the maternal SB supplement increased the concentration of non-esterified fatty acid (NEFA) in the maternal and offspring serum (P pregnancy and lactation increased the hepatic total cholesterol (Tch) content (P pregnancy and the lactation period promotes maternal fat mobilization, which may result in fatty acid uptake and lipid accumulation in the liver of the offspring.

  14. A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring.

    Science.gov (United States)

    Bayol, Stéphanie A; Farrington, Samantha J; Stickland, Neil C

    2007-10-01

    Obesity is generally associated with high intake of junk foods rich in energy, fat, sugar and salt combined with a dysfunctional control of appetite and lack of exercise. There is some evidence to suggest that appetite and body mass can be influenced by maternal food intake during the fetal and suckling life of an individual. However, the influence of a maternal junk food diet during pregnancy and lactation on the feeding behaviour and weight gain of the offspring remains largely uncharacterised. In this study, six groups of rats were fed either rodent chow alone or with a junk food diet during gestation, lactation and/or post-weaning. The daily food intakes and body mass were measured in forty-two pregnant and lactating mothers as well as in 216 offspring from weaning up to 10 weeks of age. Results showed that 10 week-old rats born to mothers fed the junk food diet during gestation and lactation developed an exacerbated preference for fatty, sugary and salty foods at the expense of protein-rich foods when compared with offspring fed a balanced chow diet prior to weaning or during lactation alone. Male and female offspring exposed to the junk food diet throughout the study also exhibited increased body weight and BMI compared with all other offspring. This study shows that a maternal junk food diet during pregnancy and lactation may be an important contributing factor in the development of obesity.

  15. Ascorbic acid co-administered with rosuvastatin reduces reproductive impairment in the male offspring from male rats exposed to the statin at pre-puberty.

    Science.gov (United States)

    Leite, Gabriel Adan Araújo; Figueiredo, Thamiris Moreira; Guerra, Marina Trevizan; Borges, Cibele Dos Santos; Fernandes, Fábio Henrique; Anselmo-Franci, Janete Aparecida; Kempinas, Wilma De Grava

    2018-05-18

    Obesity during childhood and adolescence is closely related to dysfunctions on lipid profile in children. Rosuvastatin is a statin that decreases serum total cholesterol. Ascorbic acid is an important antioxidant compound for male reproduction. Pre-pubertal male rats were distributed into six experimental groups that received saline solution 0.9% (vehicle), 3 or 10 mg/kg/day of rosuvastatin, 150 mg/day of ascorbic acid, or 3 or 10 mg/kg/day of rosuvastatin co-administered with 150 mg/day of ascorbic acid by gavage from post-natal day (PND)23 until PND53. Rats were maintained until adulthood and mated with nulliparous females to obtain the male offspring, whose animals were evaluated at adulthood in relation to reproductive parameters. This study is a follow up of a previous paper addressing potential effects on F0 generation only (Leite et al., 2017). Male offspring from rosuvastatin-exposed groups showed increased sperm DNA fragmentation, androgen depletion and impairment on the testicular and epididymal structure. Ascorbic acid coadministered to the fathers ameliorated the reproductive damage in the offspring. In summary, paternal exposure to rosuvastatin may affect the reproduction in the male offspring; however, paternal supplementation with ascorbic acid was able to reduce the reproductive impairment in the male offspring caused by statin treatment to the fathers. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Exposure of mother rats to chronic unpredictable stress before pregnancy alters the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus of offspring in early adolescence in a sexually dimorphic manner.

    Science.gov (United States)

    Huang, Yuejun; Shen, Zhiwei; Hu, Liu; Xia, Fang; Li, Yuewa; Zhuang, Jingwen; Chen, Peishan; Huang, Qingjun

    2016-12-30

    There is increasing evidence that mothers' exposure to stress before or during pregnancy is linked to an incidence of psychiatric disorders in offspring. However, a few studies have estimated the role of sex in the detrimental effects of pre-gestational stress on the offspring rats at early adolescence. Sex differences regarding the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus were investigated by MRS when the offspring rats reached 30 days. Additionally, the impact of pre-gestational stress exposed on an additional short-term acute stressor, such as forced swim, was examined in the male and female offspring rats. Our findings showed female offspring rats were more vulnerable to stressful conditions for either pre-gestational stress or acute stress in early adolescence, and had decreased GABA/Cr+PCr and Glu/Cr+PCr in the right hippocampus. Interestingly, in response to forced swim, male offspring rats whose mothers were exposed to pre-gestational stress were more affected by the short-term acute stressor and this was manifested by change of Glu/GABA and Glu/Gln in the right hippocampus. These data indicated that although female offspring rats were more vulnerable to pre-gestational stress from their mothers than males, in response to an additional acute stressor they showed better response. Therefore, both sexually dimorphic manner and combination of stressful procedures should be carefully considered in the study of stress-related psychiatric disorders in early adolescence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Sex and age-dependent effects of a maternal junk food diet on the mu-opioid receptor in rat offspring.

    Science.gov (United States)

    Gugusheff, Jessica R; Bae, Sung Eun; Rao, Alexandra; Clarke, Iain J; Poston, Lucilla; Taylor, Paul D; Coen, Clive W; Muhlhausler, Beverly S

    2016-03-15

    Perinatal junk food exposure increases the preference for palatable diets in juvenile and adult rat offspring. Previous studies have implicated reduced sensitivity of the opioid pathway in the programming of food preferences; however it is not known when during development these changes in opioid signalling first emerge. This study aimed to determine the impact of a maternal junk food (JF) diet on mu-opioid receptor (MuR) expression and ligand binding in two key regions of the reward pathway, the nucleus accumbens (NAc) and the ventral tegmental area (VTA) in rats during the early suckling (postnatal day (PND) 1 and 7) and late suckling/early post-weaning (PND 21 and 28) periods. Female rats were fed either a JF or a control diet for two weeks prior to mating and throughout pregnancy and lactation. MuR expression in the VTA was significantly reduced in female JF offspring on PND 21 and 28 (by 32% and 57% respectively, Pjunk food exposure on MuR mRNA expression or binding were detected at these time points in male offspring. These findings provide evidence that the opioid signalling system is a target of developmental programming by the end of the third postnatal week in females, but not in males. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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.

  19. Female offspring desertion and male-only care increase with natural and experimental increase in food abundance.

    Science.gov (United States)

    Eldegard, Katrine; Sonerud, Geir A

    2009-05-07

    In species with biparental care, one parent may escape the costs of parental care by deserting and leaving the partner to care for the offspring alone. A number of theoretical papers have suggested a link between uniparental offspring desertion and ecological factors, but empirical evidence is scarce. We investigated the relationship between uniparental desertion and food abundance in a natural population of Tengmalm's owl Aegolius funereus, both by means of a 5-year observational study and a 1-year experimental study. Parents and offspring were fitted with radio-transmitters in order to reveal the parental care strategy (i.e. care or desert) of individual parents, and to keep track of the broods post-fledging. We found that 70 per cent of the females from non-experimental nests deserted, while their partner continued to care for their joint offspring alone. Desertion rate was positively related to natural prey population densities and body reserves of the male partner. In response to food supplementation, a larger proportion of the females deserted, and females deserted the offspring at an earlier age. Offspring survival during the post-fledging period tended to be lower in deserted than in non-deserted broods. We argue that the most important benefit of deserting may be remating (sequential polyandry).

  20. Prenatal stress produces anxiety prone female offspring and impaired maternal behaviour in the domestic pig.

    Science.gov (United States)

    Rutherford, Kenneth M D; Piastowska-Ciesielska, Agnieszka; Donald, Ramona D; Robson, Sheena K; Ison, Sarah H; Jarvis, Susan; Brunton, Paula J; Russell, John A; Lawrence, Alistair B

    2014-04-22

    Numerous studies have shown that prenatal stress (PNS) can have profound effects on postnatal well-being. Here, the domestic pig (Sus scrofa) was used to investigate PNS effects owing to the direct relevance for farm animal welfare and the developing status of the pig as a large animal model in translational research. Pregnant primiparous sows were exposed, in mid-gestation, to either a social stressor (mixing with unfamiliar conspecifics) or were kept in stable social groups. The ratio of levels of mRNAs for corticotropin releasing hormone (CRH) receptors 1 and 2 in the amygdala, measured for the first time in the pig, was substantially increased in 10-week-old female, but not male, PNS progeny indicating a neurobiological propensity for anxiety-related behaviour. Mature female offspring were observed at parturition in either a behaviourally restrictive crate or open pen. Such PNS sows showed abnormal maternal behaviour in either environment, following the birth of their first piglet. They spent more time lying ventrally, more time standing and showed a higher frequency of posture changes. They were also more reactive towards their piglets, and spent longer visually attending to their piglets compared to controls. Associated with this abnormal maternal care, piglet mortality was increased in the open pen environment, where protection for piglets is reduced. Overall, these data indicate that PNS females have their brain development shifted towards a pro-anxiety phenotype and that PNS can be causally related to subsequent impaired maternal behaviour in adult female offspring. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

    Science.gov (United States)

    Laureano-Melo, Roberto; Império, Güínever Eustáquio do; da Silva-Almeida, Claudio; Kluck, George Eduardo Gabriel; Cruz Seara, Fernando de Azevedo; da Rocha, Fábio Fagundes; da Silveira, Anderson Luiz Bezerra; Reis, Luís Carlos; Ortiga-Carvalho, Tania Maria; da Silva Côrtes, Wellington

    2015-11-01

    Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during

  2. Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

    Directory of Open Access Journals (Sweden)

    Neil A Youngson

    2016-01-01

    Full Text Available There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16-19 weeks old, n = 14/14. A small (0.25% increase in total 5-methyl-2Ͳ-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.

  3. 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

  4. 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.

  5. Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

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    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

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

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    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

  7. Meta-analysis of paternal age and schizophrenia risk in male versus female offspring.

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    Miller, Brian; Messias, Erick; Miettunen, Jouko; Alaräisänen, Antti; Järvelin, Marjo-Riita; Koponen, Hannu; Räsänen, Pirkko; Isohanni, Matti; Kirkpatrick, Brian

    2011-09-01

    Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. There were 6 cohort studies and 6 case-control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (≥30) compared to a reference paternal age of 25-29, with no gender differences. The relative risk (RR) in the oldest fathers (≥50) was 1.66 [95% confidence interval (95% CI): 1.46-1.89, P APA (≥30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.

  8. Long-term Developmental Effects of Lactational Exposure to Lead Acetate on Ovary in Offspring Wistar Rats

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    Mehran Dorostghoal

    2011-01-01

    Full Text Available Background: During the last decades, environmental contamination by lead generated from humanactivities has become an evident concern. The present study assessed the long-term effects ofneonatal exposure to different doses of lead acetate on the ovaries of offspring rats.Materials and Methods: Pregnant female Wistar rats were randomly divided into a control andthree experimental groups. The experimental groups received 20, 100 and 300 mg/L/day leadacetate via drinking water during lactation. Ovaries of the offspring were removed at 30, 60, 90 and120 days of age, their weights recorded and fixed in Bouin’s solution. Following tissue processing,5 μm serial sections were stained with hematoxylin-eosin, and then, the numbers and diameters ofovarian follicles and corpora lutea were estimated.Results: Ovary weights decreased significantly (p<0.05 in the 300 mg/L/day dose groups at 30,60 and 90 days postnatal development. Significant dose-related decreases were seen in the numbersof primary, secondary and antral follicles in 100 (p<0.05 and 300 mg/L/day doses groups at 30and 60 days of age (p<0.01. There was significant decrease in mean number of corpora lutea inthe 100 (p<0.05 and 300 (p<0.01 mg/L/day dose groups at 60 days of age. It seems that neonatallead treatment has transient effects on follicular development in the ovary of offspring and ovarianparameters gradually improve until 90 days of age.Conclusion: The present study showed that maternal lead acetate exposure affects prepubertalovarian follicle development in a dose dependent manner, but ovarian parameters gradually improveduring the postpubertal period.

  9. Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure.

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    Treesukosol, Yada; Sun, Bo; Moghadam, Alexander A; Liang, Nu-Chu; Tamashiro, Kellie L; Moran, Timothy H

    2014-04-01

    Maternal high-fat diet appears to disrupt several energy balance mechanisms in offspring. Here, female offspring from dams fed a high-fat diet (HF) did not significantly differ in body weight compared with those fed chow (CHOW), when weaned onto chow diet. Yet when presented with both a chow and a high-fat diet, high-fat intake was significantly higher in HF compared with CHOW offspring. To assess taste-based responsiveness, offspring (12 wk old) were tested in 30-min sessions (10-s trials) to a sucrose concentration series in a brief-access taste test. Compared with CHOW, the HF offspring initiated significantly fewer trials but did not significantly differ in the amount of concentration-dependent licking. Thus, rather than affect lick response (consummatory), maternal diet affects spout approach (appetitive), which may be attributed to motivation-related mechanisms. Consistent with this possibility, naltrexone, an opioid receptor antagonist, further reduced trial initiation, but not licking in both groups. With naltrexone administration, the group difference in trial initiation was no longer evident, suggesting differences in endogenous opioid activity between the two groups. Relative expression of μ-opioid receptor in the ventral tegmental area was significantly lower in HF rats. When trial initiation was not required in one-bottle intake tests, no main effect of maternal diet on the intake of sucrose and corn oil emulsions was observed. Thus, the maternal high-fat diet-induced difference in diet preference is not likely due to changes in the sensory orosensory component of the taste stimulus but may depend on alterations in satiety signals or absorptive mechanisms.

  10. Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring.

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    Tufik, S; Fujita, K; Seabra, M de L; Lobo, L L

    1994-01-01

    Valeriana officinalis L. (Valerianaceae) is widely known to be associated with sedative properties. The effects of a valepotriates mixtures on mothers and progeny were evaluated in rats. A 30-day administration of valepotriates did not change the average length of estral cycle, nor the number of estrous phases during this period. Also, there were no changes on the fertility index. Fetotoxicity and external examination studies did not show differences, although internal examination revealed an increase in number of retarded ossification after the highest doses employed--12 and 24 mg/kg. No changes were detected in the development of the offspring after treatment during pregnancy. As for temperature, valepotriates caused a hypothermizant effect after administration by the intraperitoneal route but not after oral administration. Generally, the valepotriates employed induced some alterations after administration by the intraperitoneal route, but doses given orally were innocuous to pregnant rats and their offspring.

  11. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

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    Carolina Dizioli Rodrigues de Oliveira

    2011-09-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  12. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

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    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  13. Different combinations of maternal and postnatal diet are reflected in changes of hepatic parenchyma and hepatic TNF-alpha expression in male rat offspring.

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    Kačarević, Željka Perić; Grgić, Anđela; Šnajder, Darija; Bijelić, Nikola; Belovari, Tatjana; Cvijanović, Olga; Blažičević, Valerija; Radić, Radivoje

    2017-09-01

    Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring

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    Ong, Z. Y.; Muhlhausler, B. S.

    2011-01-01

    Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal “junk-food” diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16±0.6 vs. 11±0.8 g/kg/d; females: 19±1.3 vs. 13±0.4 g/kg/d; Pjunk-food intake in postnatal life.—Ong, Z. Y., Muhlhausler, B. S. Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. PMID:21427213

  15. Is the Performance of a Specialist Herbivore Affected by Female Choices and the Adaptability of the Offspring?

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    Tarcísio Visintin da Silva Galdino

    Full Text Available The performance of herbivorous insects is related to the locations of defenses and nutrients found in the different plant organs on which they feed. In this context, the females of herbivorous insect species select certain parts of the plant where their offspring can develop well. In addition, their offspring can adapt to plant defenses. A system where these ecological relationships can be studied occurs in the specialist herbivore, Tuta absoluta, on tomato plants. In our experiments we evaluated: (i the performance of the herbivore T. absoluta in relation to the tomato plant parts on which their offspring had fed, (ii the spatial distribution of the insect stages on the plant canopy and (iii the larval resistance to starvation and their walking speed at different instar stages. We found that the T. absoluta females preferred to lay their eggs in the tomato plant parts where their offspring had greater chances of success. We verified that the T. absoluta females laid their eggs on both sides of the leaves to better exploit resources. We also observed that the older larvae (3rd and 4th instars moved to the most nutritious parts of the plant, thus increasing their performance. The T. absoluta females and offspring (larvae were capable of identifying plant sites where their chances of better performance were higher. Additionally, their offspring (larvae spread across the plant to better exploit the available plant nutrients. These behavioral strategies of T. absoluta facilitate improvement in their performance after acquiring better resources, which help reduce their mortality by preventing the stimulation of plant defense compounds and the action of natural enemies.

  16. Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

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    Wang Fang

    2012-05-01

    Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

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

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    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.

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

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    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

  19. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

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    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

  20. Are there any remarkable effects of prenatal exposure to food colourings on neurobehaviour and learning process in rat offspring?

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    Doguc, Duygu Kumbul; Aylak, Firdevs; Ilhan, Ilter; Kulac, Esin; Gultekin, Fatih

    2015-01-01

    Artificial food colourings and additives (AFCAs) have long been discussed to have adverse effects on cognition and behaviour in children. In this study, our aim was to assess the probable side effects of prenatal exposure to colouring food additives on neurobehaviour and spatial learning process. We administered 'no observable adverse effect levels' (NOAELs) of common used AFCAs as a mixture (erythrosine, Ponceau 4R, Allura Red AC, Sunset yellow FCF, tartrazine, Amaranth, Brilliant Blue, Azorubine and Indigotine) to female rats before and during gestation and tested their effects on spatial working memory and behaviour in their offspring. Effects of AFCAs on spatial working memory were evaluated by Morris water maze, behavioural and locomotor effects by open-field and forced-swim tests. Prenatal exposure to commonly used AFCAs had no adverse effects on spatial working memory; however, assessment of interaction of sex and AFCAs on 'latency to locate the visible platform', which was used as a measure of motivation, showed a significant interaction (P < 0.05) on female rats. In addition, AFCAs caused an increase in anxiolytic like effect in the open-field test (P < 0.05) and an increase in mobility time (P < 0.05) in the forced-swim test. We also detected a significant interaction of sex and AFCAs on forced-swim test parameters (P < 0.05). These findings indicated that prenatal exposure to NOAELs of AFCAs resulted in implicit adverse effects that caused an increase in motility and a decrease in motivation and anxiety in offspring in sex-related manner.

  1. Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period.

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    Maia, Mariana Zanini; Santos, Gianne Karla; Batista, Ana Claudia Moura; Reis, Amanda Maria Sena; Silva, Juneo Freitas; Ribeiro, Lorena Gabriela Rocha; Ocarino, Natália de Melo; Serakides, Rogéria

    2016-04-01

    Objective To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day-old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7.

  2. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring.

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    Abbott, David H; Bruns, Cristin R; Barnett, Deborah K; Dunaif, Andrea; Goodfriend, Theodore L; Dumesic, Daniel A; Tarantal, Alice F

    2010-11-01

    Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155-175) days], whereas an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by cesarean section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin, and total free fatty acid (FFA) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased weight gain in infancy compared with concurrent controls. Mild to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous glucagon-tolbutamide challenge (140 days gestation), whereas excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an intravenous glucose-tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in

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

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    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.

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

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    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.

  5. 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.

  6. Gestational Protein Restriction Impairs Glucose Disposal in the Gastrocnemius Muscles of Female Rats

    Science.gov (United States)

    Blesson, Chellakkan S.; Chinnathambi, Vijayakumar; Kumar, Sathish

    2017-01-01

    Gestational low-protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring, but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP-exposed female offspring. Pregnant rats were fed a control (20% protein) or an isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months, and gastrocnemius muscles were treated with insulin ex vivo for 30 minutes. Messenger RNA and protein levels of molecules involved in insulin signaling were assessed at 4 months. LP females were smaller at birth but showed rapid catchup growth by 4 weeks. Glucose tolerance test in LP offspring at 3 months showed elevated serum glucose levels (P insulin levels. In gastrocnemius muscles, LP rats showed reduced tyrosine phosphorylation of insulin receptor substrate 1 upon insulin stimulation due to the overexpression of tyrosine phosphatase SHP-2, but serine phosphorylation was unaffected. Furthermore, insulin-induced phosphorylation of Akt, glycogen synthase kinase (GSK)–3α, and GSK-3β was diminished in LP rats, and they displayed an increased basal phosphorylation (inactive form) of glycogen synthase. Our study shows that gestational protein restriction causes peripheral insulin resistance by a series of phosphorylation defects in skeletal muscle in a mechanism involving insulin receptor substrate 1, SHP-2, Akt, GSK-3, and glycogen synthase causing dysfunctional GSK-3 signaling and increased stored glycogen, leading to distorted glucose homeostasis. PMID:28324067

  7. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    Science.gov (United States)

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-12-12

    Lead (Pb), environmentally abundant heavy-metal pollutant, is a strong toxicant for the developing central nervous system. Pb intoxication in children, even at low doses, is found to affect learning and memorizing, with devastating effects on cognitive function and intellectual development. However, the precise mechanism by which Pb impairs synaptic plasticity is not fully elucidated. The purpose of this study was to investigate the effect of pre- and neonatal exposure to low dose of Pb (with Pb concentrations in whole blood below 10μg/dL) on the synaptic structure and the pre- and postsynaptic proteins expression in the developing rat brain. Furthermore, the level of brain-derived neurotrophic factor (BDNF) was analyzed. Pregnant female Wistar rats received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring, while the control animals received drinking water. During the feeding of pups, mothers from the Pb-group were continuously receiving PbAc. Pups of both groups were weaned at postnatal day 21 and then until postnatal day 28 received only drinking water. 28-day old pups were sacrificed and the ultrastructural changes as well as expression of presynaptic (VAMP1/2, synaptophysin, synaptotagmin-1, SNAP25, syntaxin-1) and postsynaptic (PSD-95) proteins were analyzed in: forebrain cortex, cerebellum and hippocampus. Our data revealed that pre- and neonatal exposure to low dose of Pb promotes pathological changes in synapses, including nerve endings swelling, blurred and thickened synaptic cleft structure as well as enhanced density of synaptic vesicles in the presynaptic area. Moreover, synaptic mitochondria were elongated, swollen or shrunken in Pb-treated animals. These structural abnormalities were accompanied by decrease in the level of key synaptic proteins: synaptotagmin-1 in cerebellum, SNAP25 in hippocampus and syntaxin-1 in cerebellum and hippocampus. In turn, increased level of synaptophysin was

  8. A Study of Handling Cytotoxic Drugs and Risk of Birth Defects in Offspring of Female Veterinarians

    Directory of Open Access Journals (Sweden)

    Adeleh Shirangi

    2014-06-01

    Full Text Available We examined the association of occupational exposure to handling cytotoxic drugs at work with risk of birth defects among a cohort of female veterinarians. This study is a follow up survey of 321 female participants (633 pregnancies who participated in the Health Risks of Australian Veterinarian project. Data on pregnancies and exposure during each pregnancy was obtained by self-administered mailed questionnaire. Female veterinarians handling cytotoxic drugs during their pregnancy had a two-fold increased risk of birth defects in their offspring (RR = 2.08, 95% CI (1.05–4.15. Results were consistent in subgroup analysis of those who graduated during the period of 1961 to 1980 (RR = 5.04, 95% CI (1.81, 14.03 and in those working specifically in small and large animal practice. There was no increased risk in the subgroup that graduated after 1980. Women with unplanned pregnancies were more likely to handle cytotoxic drugs on a daily basis (RR = 1.86, 95% CI, 1.00–3.48 and had a higher increased risk of birth defects than those who planned their pregnancies in recent graduates and in those who worked specifically in small animal practice (RR = 2.53, 95% CI, 1.18–5.42. This study suggests that the adverse effects of handling cytotoxic drugs in pregnant women may include an increased risk of birth defects. Pregnancy intention status is an important health behavior and should be considered in prenatal programs.

  9. The effect of zinc supplementation of lactating rats on short-term and long-term memory of their male offspring.

    Science.gov (United States)

    Karami, Mohammad; Ehsanivostacolaee, Simin; Moazedi, Ali Ahmad; Nosrati, Anahita

    2013-01-01

    In this study the effect of zinc chloride (ZnCl2) administration on the short-term and long-term memory of rats were assessed. We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day) in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats' offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term) of their offspring (Plong-term) memory of all groups. Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

  10. Effect of administration of antibiotics peripartum to wistar rats on bile acid profiles in offspring

    DEFF Research Database (Denmark)

    Clement Thaarup, Ida; Roager, Henrik Munch; Tulstrup, Monica Vera-Lise

    2016-01-01

    Vertical transmission of the maternal microbiota is assumed to be crucial for the offspring’s development. A disrupted microbiota composition leading to an altered metabolic activity of the microbiota can affect bile acid profiles, which are known to influence host metabolism. Here, we examined...... whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of either amoxicillin or vancomycin to pregnant rats, influenced bile acid profiles in the offspring. The dams were treated with antibiotics from 8 days before the dams gave birth and continued until weaning (4...... weeks later). Blood samples were collected from offspring at ages 2, 4 and 14 weeks, and from dams at the end of treatment. From these blood samples, bile acids were extracted and 22 bile acids were quantified by targeted liquid chromatography mass spectrometry. Comparing the serum bile acid profiles...

  11. 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

  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.

    2017-01-01

    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

  13. [Pinealectomy and early castration in the female Wistar rat].

    Science.gov (United States)

    Slama-Scemama, A

    1976-05-17

    Pinealectomy does not significantly modify the level of pituitary and plasma gonadotropins in intact and in castrated female Rats from brith to 75 days of age. Only the weight of the thyroid gland is higher in pinealectomized rats.

  14. Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort

    DEFF Research Database (Denmark)

    Grunnet, L. G.; Hansen, S.; Hjort, L.

    2017-01-01

    and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. RESEARCH DESIGN AND METHODS: We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan...... in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. RESULTS: After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic...... glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI...

  15. 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.

  16. [Effects of perinatal exposure to bisphenol A inducing dopaminergic neuronal cell to apoptosis happening in midbrain of male rat offspring].

    Science.gov (United States)

    Lin, Yong; Zhang, Hao; Wang, Wen-dong; Wu, De-sheng; Jiang, Song-hui; Qu, Wei-dong

    2006-07-01

    To investigate the mechanism and effect of rat perinatal exposure to bisphenol A (BPA) resulting in midbrain dopaminergic neuronal cell apoptosis and tyrosine hydroxylase expression of male offspring. Rat dams were randomLy divided into 4 groups on gestational day(GD) 10 and given orally the bisphenol A doses as 0, 0.5, 5, 50 mg/kg x d from GD10 to weaning. The brains of male offspring were obtained for detecting, with immunohistochemistry protocol, the Caspase-3, Bcl-2 and tyrosine hydroxylase expression in the midbrain on postnatal day 21 or 30 respectively, and the midbrain apoptotic neuronal cell were detected by TUNEL on PND21. The expression of Caspase-3 in the midbrain of rat male offspring were increased but bcl-2 were decreased on PND21 and 30, respectively. On PND21, apoptotic neuronal cell were found in the midbrain of high and medium doses groups. TH protein expression was decreased. Perinatal exposure to bisphenol A can induce the apoptosis of midbrain dopaminergic neuron in the male rat offspring even after weaning, and concomitantly decrease the midbrain TH immunoreactivity, this may cause the abnormal function of dopaminergic pathway of rat male offspring.

  17. Disposition of inorganic mercury in pregnant rats and their offspring

    Science.gov (United States)

    Oliveira, Cláudia S.; Joshee, Lucy; Zalups, Rudolfs K.; Pereira, Maria E.; Bridges, Christy C.

    2015-01-01

    Environmental toxicants such as methylmercury have been shown to negatively impact fetal health. Despite the prevalence of inorganic mercury (Hg2+) in the environment and the ability of methylmercury to biotransform into Hg2+, little is known about the ability of Hg2+ to cross the placenta into fetal tissues. Therefore, it is important to understand the handing and disposition of Hg2+ in the reproductive system. The purpose of the current study was to assess the disposition and transport of Hg2+ in placental and fetal tissues, and to test the hypothesis that acute renal injury in dams can alter the accumulation of Hg2+ in fetal tissues. Pregnant Wistar rats were injected intravenously with 0.5 or 2.5 μmol kg−1 HgCl2 for 6 or 48 h and the disposition of Hg2+ was measured. Accumulation of Hg2+ in the placenta was rapid and dose-dependent. Very little Hg2+ was eliminated during the initial 48 h after exposure. When dams were exposed to the low dose of HgCl2, fetal accumulation of Hg2+ increased between 6 h and 48 h, while at the higher dose, accumulation was similar at each time point. Within fetal organs, the greatest concentration of Hg2+ (nmol/g) was localized in the kidneys, followed by the liver and brain. A dose-dependent increase in the accumulation of Hg2+ in fetal organs was observed, suggesting that continued maternal exposure may lead to increased fetal exposure. Taken together, these data indicate that Hg2+ is capable of crossing the placenta and gaining access to fetal organs in a dose-dependent manner. PMID:26196528

  18. Vitamin D Depletion in Pregnancy Decreases Survival Time, Oxygen Saturation, Lung Weight and Body Weight in Preterm Rat Offspring.

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    Sine Lykkedegn

    Full Text Available Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OHD determinations. After cesarean section at gestational day 19 (E19 or day 22 (E22, placental weight, birth weight, crown-rump-length (CRL, oxygenation (SaO2 at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR. S-25(OHD was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p<0.0001. Compared to the controls, E19 VDL pups had lower birth weight (2.13 vs. 2.29g, p<0.001, lung weight (0.09 vs. 0.10g, p = 0.002, SaO2 (54% vs. 69%, p = 0.002 as well as reduced survival time (0.50 vs. 1.25h, p<0.0001. At E22, the VDL-induced pulmonary differences were leveled out, but VDL pups had lower CRL (4.0 vs. 4.5cm, p<0.0001. The phospholipid levels and the surfactant protein mRNA expression did not differ between the dietary groups. In conclusion, Vitamin D depletion led to lower oxygenation and reduced survival time in the preterm offspring, associated with reduced lung weight and birth weight. Further studies of vitamin D depletion in respiratory insufficiency in preterm neonates are warranted.

  19. Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.

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    Shona L Kirk

    2009-06-01

    Full Text Available Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH, which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.

  20. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

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    Emilie Vessières

    Full Text Available Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO and control mother offspring (CMO aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life.

  1. Environmental Enrichment during Gestation Improves Behavior Consequences and Synaptic Plasticity in Hippocampus of Prenatal-Stressed Offspring Rats

    International Nuclear Information System (INIS)

    Li, Mingbo; Wang, Miao; Ding, Siqing; Li, Changqi; Luo, Xuegang

    2012-01-01

    Prenatal stress can result in various behavior deficits in offspring. Here we tested the effects of environmental enrichment during gestation used as a preventive strategy on the behavior deficits of prenatal-stressed offspring rats as well as the underlying structure basis. We compared the effect size of environmental enrichment during gestation on prenatal-stressed offspring to that of environmental enrichment after weaning. Our results showed that environmental enrichment during gestation partially prevented anxiety and the damage in learning and memory in prenatal-stressed offspring as evaluated by elevated plus-maze test and Morris water maze test. At the same time, environmental enrichment during gestation inhibited the decrease in spine density of CA1 and dentate gyrus neurons and preserved the expression of synaptophysin and glucocorticoid receptors (GRs) in the hippocampus of prenatal-stressed offspring. There was no significant difference in offspring behavior between 7-day environmental enrichment during gestation and 14-day offspring environmental enrichment after weaning. These data suggest that environmental enrichment during gestation effectively prevented the behavior deficits and the abnormal synapse structures in prenatal-stressed offspring, and that it can be used as an efficient preventive strategy against prenatal stresses

  2. Rats treated with Hypericum perforatum during pregnancy generate offspring with behavioral changes in adulthood

    Directory of Open Access Journals (Sweden)

    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.

  3. Functional adaptation in female rats: the role of estrogen signaling.

    Directory of Open Access Journals (Sweden)

    Susannah J Sample

    Full Text Available Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERβ, a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER. GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females.We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17β-estradiol, or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG gene expression of ERα, ERβ, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced.Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on adaptive bone formation in estrogen-deficient female rats.

  4. The Effect of Zinc Supplementation of Lactating Rats on Short-Term and Long-Term Memory of Their Male Offspring

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    Mohammad Karami

    2013-12-01

    Full Text Available Background: In this study the effect of zinc chloride (ZnCl2 administration on the short-term and long-term memory of rats were assessed. Methods: We enrolled six groups of adult female and control group of eight Wistar rats in each group. One group was control group with free access to food and water, and five groups drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day in drinking water for two weeks during lactation .One month after birth, a shuttle box used to short- term and long-term memory and the latency in entering the dark chamber as well. Results: This experiment showed that maternal 70 mg/kg dietary zinc during lactation influenced the working memory of rats’ offspring in all groups. Rats received 100 mg/kg/day zinc during lactation so they had significant impairment in working memory (short-term of their offspring (P<0.05. There was no significant difference in reference (long-term memory of all groups. Conclusion: Drug consumption below70 mg/kg/day zinc chloride during lactation had no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause short-term memory impairment.

  5. Asynchronous hatching provides females with a means for increasing male care but incurs a cost by reducing offspring fitness.

    Science.gov (United States)

    Ford, L E; Smiseth, P T

    2016-02-01

    In species with biparental care, sexual conflict occurs because the benefit of care depends on the total amount of care provided by the two parents while the cost of care depends on each parent's own contribution. Asynchronous hatching may play a role in mediating the resolution of this conflict over parental care. The sexual conflict hypothesis for the evolution of asynchronous hatching suggests that females adjust hatching patterns in order to increase male parental effort relative to female effort. We tested this hypothesis in the burying beetle Nicrophorus vespilloides by setting up experimental broods with three different hatching patterns: synchronous, asynchronous and highly asynchronous broods. As predicted, we found that males provided care for longer in asynchronous broods whereas the opposite was true of females. However, we did not find any benefit to females of reducing their duration of care in terms of increased lifespan or reduced mass loss during breeding. We found substantial negative effects of hatching asynchrony on offspring fitness as larval mass was lower and fewer larvae survived to dispersal in highly asynchronous broods compared to synchronous or asynchronous broods. Our results suggest that, even though females can increase male parental effort by hatching their broods more asynchronously, females pay a substantial cost from doing so in terms of reducing offspring growth and survival. Thus, females should be under selection to produce a hatching pattern that provides the best possible trade-off between the benefits of increased male parental effort and the costs due to reduced offspring fitness. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  6. 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.

  7. Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy.

    Science.gov (United States)

    Silva, Jonas G; Boareto, Ana C; Schreiber, Anne K; Redivo, Daiany D B; Gambeta, Eder; Vergara, Fernanda; Morais, Helen; Zanoveli, Janaína M; Dalsenter, Paulo R

    2017-02-22

    Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due to possible adverse effects, especially on the central nervous system. The aim of this study was to investigate the possible action of this pesticide on the behaviors related to anxiety and depression of offspring rats exposed during pregnancy. Wistar rats were treated orally with chlorpyrifos (0.01, 0.1, 1 and 10mg/kg/day) on gestational days 14-20. Male offspring behavior was evaluated on post-natal days 21 and 70 by the elevated plus-maze test, open field test and forced swimming test. The results demonstrated that exposure to 0.1, 1 or 10mg/kg/day of chlorpyrifos could induce anxiogenic-like, but not depressive-like behavior at post-natal day 21, without causing fetal toxicity. This effect was reversed on post-natal day 70. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Vitamin D metabolism impairment in the rat's offspring following maternal exposure to 137cesium.

    Science.gov (United States)

    Tissandie, E; Guéguen, Y; Lobaccaro, J M A; Grandcolas, L; Grison, S; Aigueperse, J; Souidi, M

    2009-04-01

    Previous works clearly showed that chronic contamination by 137cesium alters vitamin D metabolism. Since children are known to be a high-risk group for vitamin D metabolism disorders, effects of 137Cs on vitamin D biosynthetic pathway were investigated in newborn rats. The experiments were performed in 21-day-old male offspring of dams exposed to 137Cs in their drinking water at a dose of 6,500 Bq/l (150 Bq/rat/day) during the lactation period. Significant modifications of blood calcium (-7%, P < 0.05), phosphate (+80%, P < 0.01) and osteocalcin (-25%, P < 0.05) levels were observed in contaminated offspring, associated with an increase of blood vitamin D3 (+25%, P < 0.01). Besides, decreased expression levels of cyp2r1 and cyp27b1 (-26 and -39%, respectively, P < 0.01) were measured in liver and kidney suggesting a physiological adaptation in response to the rise in vitamin D level. Expressions of vdr, ecac1, cabp-d28k, ecac2 and cabp-9k involved in renal and intestinal calcium transport were unaffected. Altogether, these data show that early exposure to post-accidental doses of 137Cs induces the alteration of vitamin D metabolism, associated with a dysregulation of mineral homeostasis.

  9. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Shuhua; Jin, Yaping; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, College of Public Health, Shenyang, Liaoning (China); Sun, Wenjuan; Wang, Fengzhi [Shenyang Medical College, Department of Preventive Medicine, Shenyang, Liaoning (China)

    2009-06-15

    To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p<0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p<0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex. (orig.)

  10. Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

    International Nuclear Information System (INIS)

    Axelstad, Marta; Boberg, Julie; Hougaard, Karin Sorig; Christiansen, Sofie; Jacobsen, Pernille Rosenskjold; Mandrup, Karen Riiber; Nellemann, Christine; Lund, Soren Peter; Hass, Ulla

    2011-01-01

    Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T 4 ), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T 4 ) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T 4 deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and

  11. 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.

  12. Long-term effects of maternal diabetes on blood pressure and renal function in rat male offspring.

    Directory of Open Access Journals (Sweden)

    Jie Yan

    Full Text Available AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM is increasing rapidly worldwide. Previous animal models were established to study consequences of offspring after exposure to severe intrauterine hyperglycemia. In this study we are aiming to characterize the blood pressure levels and renal function of male offspring obtained from diabetic mothers with moderate hyperglycemia. METHODS: We established a rat model with moderate hyperglycemia after pregnancy by a single intraperitoneal injection of streptozotocin (STZ. The male offspring were studied and fed with either normal diet or high salt diet after weaning. Arterial pressure and renal function were measured. RESULTS: Arterial pressure of male offspring increased from 12 weeks by exposure to intrauterine moderate hyperglycemia. At 20 weeks, high salt diet accelerated the blood pressure on diabetic offspring compared to diabetic offspring fed with normal diet. We found offspring exposed to intrauterine moderate hyperglycemia had a trend to have a higher creatinine clearance rate and significant increase of urinary N-acetyl-β-D-glucosaminidase (NAG excretion indicating an early stage of nephropathy progression. CONCLUSIONS/INTERPRETATION: We observed the high blood pressure level and early renal dysfunction of male offspring obtained from diabetic mothers with moderate hyperglycemia. Furthermore, we investigated high salt diet after weaning on offspring exposed to intrauterine hyperglycemia could exacerbate the blood pressure and renal function. Renin angiotensin system (RAS plays an important role in hypertension pathogenesis and altered gene expression of RAS components in offspring with in utero hyperglycemia exposure may account for the programmed hypertension. Therefore, our study provides evidence "fetal programming" of maternal diabetes is critical for metabolic disease development.

  13. Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

    Directory of Open Access Journals (Sweden)

    Nicole L. Johnson

    2011-06-01

    Full Text Available The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1 demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration. Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

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

    Science.gov (United States)

    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

  15. 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.

  16. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    DEFF Research Database (Denmark)

    de Castro Barbosa, Thais; Ingerslev, Lars R; Alm, Petter S

    2016-01-01

    OBJECTIVES: Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. METHODS: F0-male rats fed either HFD or chow diet......1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. CONCLUSION: Our results provide insight...... into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations....

  17. The effect of sesame oil consumption during pregnancy and lactation on the memory of rat offspring in 30 days after birth

    Directory of Open Access Journals (Sweden)

    Neda Asle Iranifam

    2013-06-01

    Full Text Available Background: According to positive effect of sesame oil on the nervous system and because that fatty acids are essential for evolution of nervous system during pregnancy and for growth of neurons during lactation, in this study, effect of diet containing 10% sesame oil was evaluated on learning of rats at 30 days after birth. Material and Methods: In present study, adult female and male rats were divided into 2 groups (9 female and 3 male rats in each group: control group with usual diet and test group with diet containing 10% sesame oil were fed during pregnancy and lactation. Then male and female offspring of groups was examined at 30 days after birth using shuttle box. The results were analyzed using two way analysis of variance. Results: The average of latent time in entering to black box in start of learning in test group was less than control group (P< 0/01. The average of latent time in entering to black box at 48 after learning in test group was higher than control group and the average of spend time in black box at 48 after learning in test group was less than control group P< 0.001. Conclusion: The results showed that diet containing 10% sesame oil during pregnancy and lactation increased passive avoidance memory learning after 48 hour in rats at 30 days after birth.

  18. [Effect of selenium deficiency on the F344 inbred line offspring rats' neuro-behavior, ability of learning and memory].

    Science.gov (United States)

    Hong, Liang-Li; Tian, Dong-Ping; Su, Min; Shen, Xiu-Na; Gao, Yuxia

    2006-01-01

    To establish the selenium (Se) deficient animal model on F344 inbred line rats and observe the effects of a long-term Se-deficiency on the offspring's neuro-behavior, abilities of learning and memory. Feeding F344 inbred line rats on Se-deficient diet to establish Se-deficient animal model. For the offspring, the body weight, physiological indexes nervous reflections for growth and development were monitored during the early postnatal period. The Se-deficient diet contained less than 0.01 mg/kg and the glutathione peroxidase (GSH-Px) activity in blood of the Se-deficient group rats is lower than the Se-normal group after feeding on Se-deficient diet for 4 weeks. For the offspring, the birth weight and the body weight of Se-deficient group were obviously lower than the Se-normal group before weaning. Se-deficient offspring rats differed from Se-normal controls in lower scores in surface righting reflex (RR) test at postnatal 4th day after delivery, cliff avoidance test at postnatal 7th day and auditory acuity trial at postnatal 10th day respectively. But these differences disappear after a few days in the same tests. In addition, no significant differences between two groups in suspending test and walking ability test at postnatal 12th and 14th day. In open field test, Se-deficient male offspring stayed less time in the middle grid and moved less. In Morris water maze test, the Se-deficient offspring spent more time to find the hidden platform at the 6th and 9th training tests in the place navigation trial. Furthermore, the Se-deficient group spent less time in target quadrant when giving the spatial probe trial. A Se-deficient animal model have been established on F344 inbred line rats successfully. A long-term Se deficiency could retard the development of the offspring in uterus and after delivery. Se deficiency also decreased the offspring's abilities of spatial learning and memory in Morris water maze test and resulted in the male offspring's nervousness to new

  19. Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Beatriz Silva; Barioni, Éric Diego; Heluany, Cíntia [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Braga, Tárcio Teodoro [Department of Immunology, University of São Paulo, São Paulo (Brazil); Drewes, Carine Cristiane [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Costa, Silvia Goes [Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo (Brazil); Câmara, Niels Olsen Saraiva [Department of Immunology, University of São Paulo, São Paulo (Brazil); Farsky, Sandra Helena Poliselli [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo (Brazil); Lino-dos-Santos-Franco, Adriana, E-mail: alsantosfranco@gmail.com [Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo (Brazil)

    2016-06-01

    Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150 mg/kg, gavage) or vehicle (distilled water, gavage) 1 h before FA exposure (0.92 mg/m{sup 3}, 1 h/day, 5 days/week), for 21 days, and the 30 days old offspring were submitted to LPS injection (Salmonella abortus equi, 5 mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense. - Highlights: • FA exposure during pregnancy induces oxidative stress in the uterus. • Vitamin C treatment blunted the oxidative stress in uterus induced by FA exposure. • Oxidative stress in uterus after FA exposure impairs the immune response of offspring. • Vitamin C in pregnant rats rescued the impaired immune response in the offspring.

  20. Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring

    International Nuclear Information System (INIS)

    Ibrahim, Beatriz Silva; Barioni, Éric Diego; Heluany, Cíntia; Braga, Tárcio Teodoro; Drewes, Carine Cristiane; Costa, Silvia Goes; Câmara, Niels Olsen Saraiva; Farsky, Sandra Helena Poliselli; Lino-dos-Santos-Franco, Adriana

    2016-01-01

    Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150 mg/kg, gavage) or vehicle (distilled water, gavage) 1 h before FA exposure (0.92 mg/m 3 , 1 h/day, 5 days/week), for 21 days, and the 30 days old offspring were submitted to LPS injection (Salmonella abortus equi, 5 mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense. - Highlights: • FA exposure during pregnancy induces oxidative stress in the uterus. • Vitamin C treatment blunted the oxidative stress in uterus induced by FA exposure. • Oxidative stress in uterus after FA exposure impairs the immune response of offspring. • Vitamin C in pregnant rats rescued the impaired immune response in the offspring.

  1. Hypotrophy of conduit artery walls of the offspring of nitric oxide-defective rats

    Directory of Open Access Journals (Sweden)

    Kristek F.

    2004-01-01

    Full Text Available The objective of the present study was to investigate the structure of the arterial walls of the offspring stemming from nitric oxide (NO-defective hypertensive parents. The parents were treated with N G-nitro-L-arginine methyl ester (40 mg kg-1 day-1 for 5 weeks. Blood pressure was measured noninvasively in six 30-day-old rats and nine age-matched controls. The cardiovascular system was perfused with glutaraldehyde at 120 mmHg. The thoracic aorta and carotid artery were processed for electron microscopy, and geometry was determined by light microscopy. Endothelial cells, smooth muscle cells (SMC and extracellular matrix (ECM were determined by the point counting method in electron micrographs of the carotid artery. The blood pressure of experimental offspring was 150.0 ± 2.3 vs 104.6 ± 2.1 mmHg (P < 0.01 for the controls and their heart/body weight ratio of 3.9 ± 0.1 vs 4.4 ± 0.2 (P < 0.05 for the controls indicated cardiac hypotrophy. The wall thickness (tunica intima and media of the thoracic aorta and carotid artery of experimental offspring was decreased to 78.9% (P < 0.01 and 83.8% (P < 0.01, respectively, compared to controls, as confirmed by a respective cross-sectional area of 85.3% (P < 0.01 and 84.1% (P < 0.01. The wall thickness/inner diameter ratio was reduced to 75% (P < 0.01 in the thoracic artery and to 81.5% (P < 0.01 in the carotid artery. No change in endothelial cell volume density or ECM was observed in the tunica intima of the carotid artery, and SMC volume density was lower in the tunica media (37.6 ± 0.9 vs 44.7 ± 1.1% for controls, P < 0.01, indicating compromised SMC development. Interference with arginine metabolism, a decrease in NO, and other factors are possible mechanisms underlying the structural alterations of the cardiovascular system of offspring from NO-defective hypertensive rats.

  2. Effects of pre- and postnatal litter size reduction on development and behavior of rat offspring.

    Science.gov (United States)

    Milković, K; Paunović, J; Joffe, J M

    1976-07-01

    Litter size was reduced to 2-5 rat pups either prenatally by unilateral maternal oviduct ligation (Group PRN) or postnatally by removing pups (Group PST). Normal size litters (8-10 pups) of sham ligated (SHM) and intact (CON) mothers served as controls. Weights at 30 days were increased by prenatal or postnatal reduction and reduced by prenatal stress (SHM); the sex difference in weight was most pronounced in PRN rats. At 75 days PRN rats were heaviest, with no differences between the other groups. Relative ovarian weights were reduced in PRN females and absolute testes weights increased in PST males. The PRN and SHM females had smaller relative adrenal weights than CON and PST females. Open-field activity was generally increased by prior avoidance conditioning and effects of treatments were found only in groups tested after avoidance-conditioning: PRN and SHM rats were more active than PST and CON rats, particularly on Days 1 (SHM) and 4 (SHM and PRN) of testing. Passive-avoidance behavior of PRN rats was also more susceptible to previous test experience: they emerged more slowly if they had prior open-field experience. The PST animals, in contrast, emerged more rapidly after prior test experience. Plasma corticosterone levels and shuttlebox conditioning and extinction were unaffected by treatments.

  3. Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring

    International Nuclear Information System (INIS)

    Lundberg, Rebecca; Lyche, Jan L.; Ropstad, Erik; Aleksandersen, Mona; Roenn, Monika; Skaare, Janneche U.; Larsson, Sune; Orberg, Jan; Lind, P. Monica

    2006-01-01

    The aim of this study was to investigate if environmentally relevant doses of the putative estrogenic non dioxin-like PCB 153 and the dioxin-like PCB 126 caused changes in bone tissue in female goat offspring following perinatal exposure. Goat dams were orally dosed with PCB 153 in corn oil (98 μg/kg body wt/day) or PCB 126 (49 ng/kg body wt/day) from day 60 of gestation until delivery. The offspring were exposed to PCB in utero and through mother's milk. The suckling period lasted for 6 weeks. Offspring metacarpal bones were analysed using peripheral quantitative computed tomography (pQCT) after euthanisation at 9 months of age. The diaphyseal bone was analysed at a distance of 18% and 50% of the total bone length, and the metaphyseal bone at a distance of 9%. Also, biomechanical three-point bending of the bones was conducted, with the load being applied to the mid-diaphyseal pQCT measure point (50%). PCB 153 exposure significantly decreased the total cross-sectional area (125 mm 2 ± 4) versus non-exposed (142 mm 2 ± 5), decreased the marrow cavity (38 mm 2 ± 4) versus non-exposed (50 mm 2 ± 3) and decreased the moment of resistance (318 mm 3 ± 10) versus non-exposed (371 mm 3 ± 20) at the diaphyseal 18% measure point. At the metaphyseal measure point, the trabecular bone mineral density (121 mg/cm 3 ± 5) was increased versus non-exposed (111 mg/cm 3 ± 3). PCB 126 exposure did not produce any observable changes in bone tissue. The biomechanical testing of the bones did not show any significant changes in bone strength after PCB 153 or PCB 126 exposure. In conclusion, perinatal exposure to PCB 153, but not PCB 126, resulted in altered bone composition in female goat offspring

  4. Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

    Energy Technology Data Exchange (ETDEWEB)

    Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology

    2010-09-15

    The purpose of the investigation is to reveal the mechanism of the decreased ability of learning and memory induced by coal burning fluorosis. Ten offspring SD rats aged 30 days, who were born from the mothers with chronic coal burning fluorosis, and ten offspring with same age from the normal mothers as controls were selected. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. Cholinesterase activity was detected by photometric method. The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha 3, alpha 4 and alpha 7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha 3 and alpha 4 nAChRs were decreased, whereas the alpha 7 mRNA increased. The data indicated that coal burning fluorosis can induce the decreased ability of learning and memory of rat offspring, in which the mechanism might be connected to the changed nAChRs and cholinesterase.

  5. 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

  6. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning

    Science.gov (United States)

    In utero exposure to maternal obesity increases the offspring’s risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND) 21. In the current s...

  7. 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

  8. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

    Science.gov (United States)

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

    2014-06-01

    Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  9. Dextromethorphan attenuated the higher vulnerability to inflammatory thermal hyperalgesia caused by prenatal morphine exposure in rat offspring

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    Chen Chien-Fang

    2011-08-01

    Full Text Available Abstract Background Co-administration of dextromethorphan (DM with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on inflammatory hyperalgesia in morphine-exposed offspring. Therefore, we attempt to investigate the possible effect of prenatal morphine exposure on the vulnerability to hyperalgesia and the possible therapeutic effect of DM in the present study. Methods Fifty μl of carrageenan (20 mg/ml was injected subcutaneously into the plantar surface of the right hind paw in p18 rats to induce hyperalgesia. Mean paw withdrawal latency was measured in the plantar test to index the severity of hyperalgesia. Using Western blotting and RT-PCR, the quantitative analyses of NMDA receptor NR1 and NR2B subunits were performed in spinal cords from different groups of animals. Results In the carrageenan-induced hyperalgesia model, rat offspring passively exposed to morphine developed a severe hyperalgesia on postnatal day 18 (p18, which also had a more rapid time course than those in the controls. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Western blot and RT-PCR analysis showed that the levels of protein and mRNA of NMDA receptor NR1 and NR2B subunits were significantly higher in the lumbar spinal cords of rats (p14 exposed to prenatal morphine; the co-administration of DM could reverse the effect of morphine on NR1 and attenuate the effect on NR2B. Conclusions Thus, DM may have a great potential in the prevention of higher vulnerability to inflammatory thermal hyperalgesia in the offspring of morphine-addicted mothers.

  10. Vaginal thread formation in the healthy offspring of untreated Long-Evans rats

    Science.gov (United States)

    Vaginal threads are characterized as cords of mesenchymal tissue that cross the vaginal opening. They are sometimes apparent in rats after weaning, and typically disappear within 1-2 days as the female reaches puberty. If persistent, they can increase uncertainty in assessing rep...

  11. Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

    Science.gov (United States)

    Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

    2016-01-15

    Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. 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.

  13. Signs of a higher prevalence of autoimmune thyroiditis in female offspring of bipolar parents

    NARCIS (Netherlands)

    Hillegers, Manon H. J.; Reichart, Catrien G.; Wals, Marjolein; Verhulst, Frank C.; Ormel, Johan; Nolen, Willem A.; Drexhage, Hemmo A.

    2007-01-01

    Background: Studies are inconsistent as to whether patients with bipolar disorder are more frequently affected by autoimmune thyroiditis. Aim: To study the prevalence of autoimmune thyroiditis in offspring of bipolar patients. Method: In 1998 140 children (age 12-21 years) of bipolar parents were

  14. 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.

  15. Maternal "junk-food" feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.

    Science.gov (United States)

    Ong, Z Y; Muhlhausler, B S

    2011-07-01

    Individuals exposed to high-fat, high-sugar diets before birth have an increased risk of obesity in later life. Recent studies have shown that these offspring exhibit increased preference for fat, leading to suggestions that perinatal exposure to high-fat, high-sugar foods results in permanent changes within the central reward system that increase the subsequent drive to overconsume palatable foods. The present study has determined the effect of a maternal "junk-food" diet on the expression of key components of the mesolimbic reward pathway in the offspring of rat dams at 6 wk and 3 mo of age. We show that offspring of junk-food-fed (JF) dams exhibit higher fat intake from weaning until at least 3 mo of age (males: 16 ± 0.6 vs. 11 ± 0.8 g/kg/d; females: 19 ± 1.3 vs. 13 ± 0.4 g/kg/d; Pjunk-food intake in postnatal life.

  16. Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood.

    Science.gov (United States)

    Senko, Tomáš; Svitok, Pavel; Kršková, Lucia

    2017-10-01

    The intrauterine condition in which the mammalian foetus develops has an important role in prenatal programming. The aim of this study was to determine the extent to which activation of the maternal renin-angiotensin-aldosterone system (RAAS) could influence social behaviour strategies in offspring via changes in social neurotransmitters in the brain. Pregnant female Wistar rats were implanted with osmotic minipumps which continually released angiotensin II for 14 days at concentration of 2 μg/kg/h. The adult offspring (angiotensin and control groups) underwent a social interaction test. The mRNA expression of vasopressin, oxytocin and the oxytocin receptor in selected brain areas was measured by in situ hybridisation. Prenatal exposure to higher levels of angiotensin II resulted in a strong trend toward decreased total social interaction time and significantly decreased time spent in close proximity and frequency of mutual sniffing. The angiotensin group showed no changes in oxytocin mRNA expression in the hypothalamic paraventricular or supraoptic nuclei, but this group had reduced vasopressin mRNA expression in the same areas. We concluded that maternal activation of RAAS (via higher levels of angiotensin II) caused inhibition of some socio-cohesive indicators and decreased vasopressinergic activity of offspring. Taken together, these results suggest a reactive rather than proactive social coping strategy.

  17. Dose dependent transfer of 203lead to milk and tissue uptake in suckling offspring studied in rats and mice

    International Nuclear Information System (INIS)

    Palminger Hallen, I.; Oskarsson, A.

    1993-01-01

    The dose-dependent transfer of 203 Pb to milk and uptake in suckling rats and mice during a three-day nursing period was studied. On day 14 of lactation, the dams were administered a single intravenous dose of lead, labelled with 203 Pb, in four or five doses from 0.0005 to 2.0 mg Pb/kg b.wt. There was a linear relationship between Pb levels in plasma and milk of both species. The Pb milk: plasma ratios at 24 hr after administration were 119 and 89 in mice and rats, respectively. At 72 hr the Pb milk: plasma ratio had decreased to 72 in mice and 35 in rats. The tissue levels of lead in the suckling rats and mice were also linearly correlated with lead concentration in milk at 72 hr, showing that milk could be used as an indicator of lead exposure to the suckling offspring. It is concluded that lead is transported into rat and mouse milk to a very high extent and the excretion into milk is more efficient in mice than in rats. On the other hand, rat pups had higher lead levels in tissues than mice pups, which might be due to a higher bioavailability and/or a lower excretion of lead in rat pups. Thus, lead in breast milk could be used as a biological indicator of lead exposure in the mother as well as in the suckling offspring. (au) (38 refs.)

  18. Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2014-07-01

    In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5α-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. © 2014 Society for Endocrinology.

  19. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    Science.gov (United States)

    Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Effects of a high-fat diet during pregnancy and lactation are modulated by E. coli in rat offspring.

    Science.gov (United States)

    Fåk, F; Karlsson, C L J; Ahrné, S; Molin, G; Weström, B

    2012-05-01

    Microbial manipulations in early life can affect gut development and inflammatory status of the neonate. The maternal diet during pregnancy and lactation also influences the health of the offspring, but the impact of maternal high-fat (HF) feeding along with modulations of the gut microbiota on body weight, fat deposition and gut function in the offspring has been poorly studied. Rat dams were given access to either an HF or a standard low-fat diet during the last 2 weeks of pregnancy and during lactation and effects on body weight and gastrointestinal function were investigated in the 14-day-old offspring. To elucidate whether bacterial administration to the dam could modulate any effects of the diets in the rat pups, another group of dams were given Escherichia coli in their drinking water. Maternal HF feeding resulted in increased body and fat pad weights in the offspring, along with increased levels of the acute-phase protein, haptoglobin and decreased protein content and disaccharidase activities in the small intestine. The addition of E. coli further accentuated these responses in the young rats, which, in addition to higher body weights and increased fat deposition, also showed an increased intestinal permeability and elevated levels of haptoglobin. The present study demonstrates for the first time how bacterial administration to the maternal diet during the neonatal period can affect body weight and fat deposition in the offspring. The results point to a mechanistic link between the gut microbiota, increased intestinal permeability and metabolic endotoxemia, which appear to have led to increased adiposity in the young rats.

  1. Development of rat female genital cortex and control of female puberty by sexual touch.

    Directory of Open Access Journals (Sweden)

    Constanze Lenschow

    2017-09-01

    Full Text Available Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  2. Development of rat female genital cortex and control of female puberty by sexual touch.

    Science.gov (United States)

    Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

    2017-09-01

    Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  3. Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

    Directory of Open Access Journals (Sweden)

    Romana Šlamberová

    2014-01-01

    Full Text Available The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA exposure to adult amphetamine (AMP treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed were administered with AMP (5 mg/kg or saline (1 ml/kg in adulthood. Behaviour in unknown environment was examined in open field test (Laboras, active drug-seeking behaviour in conditioned place preference test (CPP, spatial memory in the Morris water maze (MWM, and levels of corticosterone (CORT were analyzed by enzyme immunoassay (EIA. Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  4. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    International Nuclear Information System (INIS)

    Grassi, Tony F.; Silva, Glenda N. da; Bidinotto, Lucas T.; Rossi, Bruna F.; Quinalha, Marília M.; Kass, Laura; Muñoz-de-Toro, Mónica; Barbisan, Luís F.

    2016-01-01

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  5. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Tony F. [UNESP – Univ. Estadual Paulista, Botucatu Medical School, Department of Pathology, Botucatu, SP (Brazil); Silva, Glenda N. da [UFOP – Federal University of Ouro Preto, Analysis Clinical Department, Ouro Preto, MG (Brazil); Bidinotto, Lucas T. [Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP (Brazil); Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP (Brazil); Rossi, Bruna F.; Quinalha, Marília M. [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil); Kass, Laura; Muñoz-de-Toro, Mónica [UNL – Universidad Nacional del Litoral, School of Biochemistry and Biological Sciences, Human Pathology Department, Instituto de Salud y Ambiente del Litoral (ISAL, CONICET-UNL), Santa Fe (Argentina); Barbisan, Luís F., E-mail: barbisan@ibb.unesp.br [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil)

    2016-07-15

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  6. 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.

  7. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

    Science.gov (United States)

    Ehrlich, David E.; Neigh, Gretchen N.; Bourke, Chase H.; Nemeth, Christina L.; Hazra, Rimi; Ryan, Steven J.; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney; Rainnie, Donald G.; Stowe, Zachary N.; Owens, Michael J.

    2015-01-01

    Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436

  8. High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring

    Science.gov (United States)

    The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosi...

  9. In vivo longitudinal micro-CT study of bent long limb bones in rat offspring.

    Science.gov (United States)

    De Schaepdrijver, Luc; Delille, Peter; Geys, Helena; Boehringer-Shahidi, Christian; Vanhove, Christian

    2014-07-01

    Micro-computed X-ray tomography (micro-CT) has been reported as a reliable method to assess ex vivo rat and rabbit fetal skeletons in embryo-fetal developmental toxicity studies. Since micro-CT is a non-invasive imaging modality it has the potential for longitudinal, in vivo investigation of postnatal skeletal development. This is the first paper using micro-CT to assess the reversibility of drug-induced bent long bones in a longitudinal study from birth to early adulthood in rat offspring. Analysis of the scans obtained on postnatal Day 0, 7, 21 and 80 showed complete recovery or repair of the bent long limb bones (including the scapula) within the first 3 weeks. When assessing risk the ability to demonstrate recovery is highly advantageous when interpreting such transient skeletal change. In summary, in vivo micro-CT of small laboratory animals can aid in non-clinical safety assessment, particularly for specific mechanistic purposes or to address a particular concern in developmental biology. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. 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.

  11. Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

    Directory of Open Access Journals (Sweden)

    Sam Jun Lee

    2016-05-01

    Full Text Available Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF and tyrosine kinase B (TrkB levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats.

  12. Females of the communally breeding rodent, Octodon degus, transfer antibodies to their offspring during pregnancy and lactation.

    Science.gov (United States)

    Becker, María Inés; De Ioannes, Alfredo E; León, Cecilia; Ebensperger, Luis A

    2007-06-01

    Females in numerous rodent species engage in communal nesting and breeding, meaning that they share a nest to rear their young together. One potential benefit to communally nesting mothers is that infants improve their immunocompetence. Thus, suckling from two or more females might provide newborns with a more diverse array of antibodies and defensive cells. As a first step toward testing the immunocompetence hypothesis, we assessed whether female degus (Octodon degus), a communally nesting and breeding caviomorph rodent, transfer immunoglobulins to their young through the yolk sac or placenta while in the uterus and, during lactation, through milk. With this aim, adult degu females were immunized with four antigens, including two mollusk hemocyanins from Concholepas and Megathura (CCH and KLH, respectively), porcine thyroglobulin and tetanus toxoid. Specific antibodies against the experimental antigens were used to track the origin of antibodies in the young. To establish the presence of specific antibodies of IgG and IgA isotypes in sera and milk of animals, an indirect enzyme-linked immunosorbent assay (ELISA) was developed. Degu females produced specific antibodies against antigens not found in their natural environment, and mothers were able to transfer the induced antibodies to their litters during pregnancy (IgG) and during lactation (IgA). However, we recorded only limited evidence of degu offspring acquiring antibodies from lactating mothers other than their own, giving little support to the increased immunocompetence hypothesis.

  13. 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.

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    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.

  14. Comparative toxicology of carfene in male and female rats

    International Nuclear Information System (INIS)

    Hassanin, M.M.; Tawfik, S.M.F.

    2005-01-01

    The objective of this study was to determine the potential toxicity associated with daily oral administrations of carfene (2.5 mg/kg body weight) for 15 consecutive days on protein level in liver, kidney, brain and spleen tissues of male and female rats after 1, 5, 10 and 15 days of treatment. Evaluation of the trace elements, zinc and copper in serum, revealed that zinc level was decreased significantly while that of copper was increased in both male and female rats compared to controls. The incorporation rate of 14 C-isoleucine for synthesis of protein tended to decrease in liver tissues and increase in brain tissues of rats. Kidney and spleen tissues showed fluctuated changes. It was noticed in the present investigation that the incorporation rate of I4 C-radioactivity in different selected tissues under estimation was more pronounced in male than in female rats

  15. Perinatal BPA Exposure Induces Hyperglycemia, Oxidative Stress and Decreased Adiponectin Production in Later Life of Male Rat Offspring

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    Shunzhe Song

    2014-04-01

    Full Text Available The main object of the present study was to explore the effect of perinatal bisphenol A (BPA exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  16. Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: II-the developmental pattern of neurons in relation to oxidative stress and antioxidant defense system.

    Science.gov (United States)

    Ahmed, O M; Ahmed, R G; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M

    2012-10-01

    Excessive concentrations of free radicals in the developing brain may lead to neurons maldevelopment and neurons damage and death. Thyroid hormones (THs) states play an important role in affecting the modulation of oxidative stress and antioxidant defense system. Thus, the objective of this study was to clarify the effect of hypothyroidism and hyperthyroidism in rat dams on the neurons development of different brain regions of their offspring at several postnatal weeks in relation to changes in the oxidative stress and antioxidant defense system. The adult female rats were administered methimazole (MMI) in drinking water (0.02% w/v) from gestation day 1 to lactation day 21 to induce hypothyroidism and exogenous thyroxine (T4) in drinking water (0.002% w/v) beside intragastric incubation of 50--200 T4 μg/kg body weight (b. wt.) to induce hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and total triiodothyronine (TT3) levels were detectably increased at day 10 post-partum than those at day 10 of pregnancy. Free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations in normal offspring were elevated at first, second and third postnatal weeks in an age-dependent manner. In hypothyroid group, a marked depression was observed in sera of dam TT3 and TT4 as well as offspring FT3, FT4 and GH, while there was a significant increase in TSH level with the age progress. The reverse pattern to latter state was recorded in hyperthyroid group. Concomitantly, in control offspring, the rate of neuron development in both cerebellar and cerebral cortex was increased in its density and complexity with age progress. This development may depend, largely, on THs state. Both maternal hypothyroidism and hyperthyroidism caused severe growth retardation in neurons of these regions of their offspring from the first to third weeks. Additionally, in normal offspring, seven antioxidant enzymes, four non-enzymatic antioxidants

  17. Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty

    International Nuclear Information System (INIS)

    Abdel-Rahman, Ali; Dechkovskaia, Anjelika M.; Sutton, Jazmine M.; Chen, Wei-Chung; Guan, Xiangrong; Khan, Wasiuddin A.; Abou-Donia, Mohamed B.

    2005-01-01

    Maternal smoking during pregnancy is known to be a significant contributor to developmental neurological health problems in the offspring. In animal studies, nicotine treatment via injection during gestation has been shown to produce episodic hypoxia in the developing fetus. Nicotine delivery via mini osmotic pump, while avoiding effects due to hypoxia-ischemia, it also provides a steady level of nicotine in the plasma. In the present study timed-pregnant Sprague-Dawley rats (300-350 g) were treated with nicotine (3.3 mg/kg, in bacteriostatic water via s.c. implantation of mini osmotic pump) from gestational days (GD) 4-20. Control animals were treated with bacteriostatic water via s.c. implantation of mini osmotic pump. Offspring on postnatal day (PND) 30 and 60, were evaluated for changes in the ligand binding for various types of nicotinic acetylcholine receptors and neuropathological alterations. Neurobehavioral evaluations for sensorimotor functions, beam-walk score, beam-walk time, incline plane and grip time response were carried out on PND 60 offspring. Beam-walk time and forepaw grip time showed significant impairments in both male and female offspring. Ligand binding densities for [ 3 H]epibatidine, [ 3 H]cytisine and [ 3 H]α-bungarotoxin did not show any significant changes in nicotinic acetylcholine receptors subtypes in the cortex at PND 30 and 60. Histopathological evaluation using cresyl violet staining showed significant decrease in surviving Purkinje neurons in the cerebellum and a decrease in surviving neurons in the CA1 subfield of hippocampus on PND 30 and 60. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer of cerebellum and the CA1 subfield of hippocampus on PND 30 and 60 of both male and female offspring. These results indicate that maternal exposure to nicotine produces significant neurobehavioral deficits, a decrease in the surviving neurons and an

  18. LHRH and LH in peripubertal female rats following prenatal and/or postnatal ethanol exposure

    International Nuclear Information System (INIS)

    Morris, D.L.; Harms, P.G.; Petersen, H.D.; McArthur, N.H.

    1989-01-01

    The effects of pre- and postnatal exposure to ethanol (ETHO) on LHRH and LH were investigated. Pregnant and/or lactating dams were fed ETHOD during: (1) gestation, (2) lactation, or (3) gestation-lactation. Female offspring were decapitated at 30 or 40 days-of-age; trunk blood was collected for plasma LH RIA; and hypothalamic tissues were collected for LHRH RIA. Hypothalamic LHRH content of all ETOH-exposed groups was less than that of non-ETOH-fed controls at 30 and 40 days-of-age. Plasma LH concentrations of all ETOH-exposed groups were less than those of non-ETOD-fed controls at 30 and 40 days-of-age. Also, at 30 and 40 days-of-age, the plasma LH concentrations of the animals exposed to ETOH during lactation and gestation-lactation were less than those of the animals exposed to ETOH during gestation. These data suggest that ETOH exposure during gestation and/or lactation negatively affects hypothalamic LHRH content of femal rat offspring. Decreased hypothalamic LHRH content with corresponding lowered plasma LH concentration suggests that ETOH influences development or maturation of hypothalamic LHRH neurons by possibly decreasing their number or synthesizing capability

  19. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation

    International Nuclear Information System (INIS)

    Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    Highlights: • The effect of maternal exposure to HCP on rat hippocampal neurogenesis was examined. • HCP induces myelin vacuolation of nerve tracts in the septal–hippocampal pathway. • Myelin changes suppress Chrnb2-mediated cholinergic inputs to the dentate gyrus. • SGZ apoptosis occurs via the mitochondrial pathway and targets type-2b cells. • Dysfunction of cholinergic inputs is related to type-2b SGZ cell apoptosis. - Abstract: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction

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

    OpenAIRE

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    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 ...

  1. Effect of zinc supplementation of pregnant rats on short-term and long-term memory of their offspring

    International Nuclear Information System (INIS)

    Ali, M.A.; Ghotbeddin, Z.; Parham, G.H.

    2007-01-01

    To see the dose dependent effects of zinc chloride on the short-term and long-term memory in a shuttle box (rats). Six pair adult wistar rats were taken for this experiment. One group of pregnant rats received a daily oral dose of 20 mg/kg Zn as zinc chloride and the remaining groups received a daily oral dose of (30, 50, 70,100 mg/kg) zinc chloride for two weeks by gavage. One month after birth, a shuttle box was used to test short-term and long-term memory. Two criteria were considered to behavioral test, including latency in entering dark chamber and time spent in the dark chamber. This experiment showed that oral administration of ZnCl/sub 2/ with (20, 30, 50 mg/kg/day) doses after 2 weeks at the stage of pregnancy, can improve the working memory of their offspring (p<0.05). Where as ZnCl/sub 2/ with 30 mg/kg/day dose has been more effective than other doses (p<0.001). But rat which received ZnCl/sub 2/ with 100 mg/kg/day at the stage of pregnancy, has shown significant impairment in working (short-term) memory of their offspring (p<0.05) and there was no significant difference in reference (long-term) memory 3 for any of groups. This study has demonstrated that zinc chloride consumption with 30 mg/kg/day dose for two weeks at the stage of pregnancy in rats, has positive effect on short-term memory on their offspring. But consumption of enhanced zinc 100 mg/kg/day in pregnant rats can cause short-term memory impairment. On the other hand, zinc supplementation such as zinc chloride has no effect on long-term memory. (author)

  2. Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring.

    Science.gov (United States)

    Grote, Konstanze; Hobler, Carolin; Andrade, Anderson J M; Grande, Simone Wichert; Gericke, Christine; Talsness, Chris E; Appel, Klaus E; Chahoud, Ibrahim

    2007-09-05

    The organotin compound (OTC) triphenyltin (TPT) is used extensively as a herbicide, pesticide and fungicide in agriculture as well as, together with tributyltin (TBT), in marine antifouling paints. We studied the effects of in utero exposure to 2 or 6 mg triphenyltinchloride (TPTCl)/kgb.w. on pregnancy outcome and postnatal development in rat offspring. Gravid Wistar rats were treated per gavage from gestational day 6 until the end of lactation. In the 6 mg TPTCl dose group gestational mortality in dams as well as an increased incidence of anticipated and delayed parturition was observed. Furthermore, treatment resulted in a significant increase in perinatal mortality, a decrease in lactational body weight gain as well as in delayed physical maturation of offspring. Similarily, exposure to 2mg TPTCl/kgb.w. resulted in a significant increase in perinatal mortality and in delayed eye opening. Lactational body weight gain and other landmarks of physical maturation were unaffected in the low dose group. We conclude, that in utero exposure to TPTCl at the described dose levels severely affected pregnancy outcome and perinatal survival of offspring. These results were unexpected, as in two earlier studies with pubertal rats TPTCl at the same dose levels no signs of general toxicity were observed.

  3. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  4. Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

    Science.gov (United States)

    Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

  5. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    Energy Technology Data Exchange (ETDEWEB)

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India); Parmar, Devendra [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India)

    2007-12-15

    Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

  6. Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane

    International Nuclear Information System (INIS)

    Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

    2007-01-01

    Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD 50 ) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring

  7. High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring.

    Science.gov (United States)

    Sánchez-Hernández, Diana; Poon, Abraham N; Kubant, Ruslan; Kim, Hwanki; Huot, Pedro S P; Cho, Clara E; Pannia, Emanuela; Reza-López, Sandra A; Pausova, Zdenka; Bazinet, Richard P; Anderson, G Harvey

    2016-01-01

    High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid.

    Science.gov (United States)

    Gao, Jingquan; Wu, Hongmei; Cao, Yonggang; Liang, Shuang; Sun, Caihong; Wang, Peng; Wang, Ji; Sun, Hongli; Wu, Lijie

    2016-09-01

    Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal VPA-induced brain dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning.

    Directory of Open Access Journals (Sweden)

    Sarah J Borengasser

    Full Text Available In utero exposure to maternal obesity increases the offspring's risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams at PND21. Indirect calorimetry revealed decreases in energy expenditure (p<0.001 and increases in RER values (p<0.001, which were further exacerbated by high fat diet (45% kcals from fat consumption indicating an impaired ability to utilize fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial function is known to be associated with fatty acid oxidation (FAO in the liver. Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p = 0.012 and mitochondrial protein content (p = 0.002, electron transport chain complexes (II, III, and ATPase, and fasting PGC-1α mRNA expression (p<0.001. Moreover, hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p<0.001 but was also hyperacetylated in offspring of obese dams (p<0.005 suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduces hepatic fatty acid oxidation and precedes the development of detrimental obesity associated co-morbidities such as insulin resistance and NAFLD.

  10. Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression.

    Science.gov (United States)

    Zhang, X G; Zhang, H; Liang, X L; Liu, Q; Wang, H Y; Cao, B; Cao, J; Liu, S; Long, Y J; Xie, W Y; Peng, D Z

    2016-08-19

    Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) were performed on the offsprings 30 days after birth. The results showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of whole-genome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.

  11. A female melanin ornament signals offspring fluctuating asymmetry in the barn owl

    NARCIS (Netherlands)

    Roulin, A; Ducrest, AL; Balloux, F; Dijkstra, Cornelis; Riols, C

    2003-01-01

    Sexual selection theory predicts that males advertise quality by displaying extravagant ornaments. By contrast, whether phenotypic variation in females has a signalling function remains an open question. Here, to our knowledge, we provide the first evidence that a female plumage trait can signal

  12. The role of social environment on parental care: offspring benefit more from the presence of female than male helpers.

    Science.gov (United States)

    Brouwer, Lyanne; van de Pol, Martijn; Cockburn, Andrew

    2014-03-01

    Investment in offspring depends on the costs and benefits to the carer, which can vary with sex and social status. Investment also depends on the effort of others by allowing for compensation (load-lightening), with biparental care studies showing that this depends on the state and type of the other carer. By contrast, studies on cooperative breeders have solely focussed on the effects of group size rather than its composition (i.e. social environment). Here we propose and provide the first test of the 'Social Environment' hypothesis, that is, how the characteristics (here the sex) of other helpers present in the group affect parental care and how this in turn affects offspring fitness in cooperatively breeding red-winged fairy-wrens (Malurus elegans). Breeders provisioned nestlings at a higher rate than helpers, but there was no sex difference in provisioning rate. Compensation to increasing group size varied little with sex and status, but strongly depended on social environment. All group members reduced their provisioning rates in response to an increasing number of male (load-lightening), but not female helpers (additive care). As a result, nestlings received more food and grew faster in the presence of female helpers. The increased nestling growth did convey a fitness advantage due to a higher post-fledging survival to adulthood. Our study provides the first evidence that parental care can depend on social environment. This could be an important overlooked aspect to explain variation in parental care in cooperative breeders in general and in particular the enormous variation between the sexes, which we reveal in a literature overview. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

  13. Low dose prenatal ethanol exposure induces anxiety-like behaviour and alters dendritic morphology in the basolateral amygdala of rat offspring.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control or 6% (vol/vol ethanol (EtOH throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult or 15 months (Aged of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety - like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour.

  14. 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.

  15. Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

    Science.gov (United States)

    Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

    2016-03-01

    The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

  17. Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats

    DEFF Research Database (Denmark)

    Hougaard, K.S.; Mandrup, Karen; Kjaer, S.L.

    2011-01-01

    An increasing number of scientific studies indicate that maternal stress during pregnancy influences fetal development of the nervous system and thereby the behavioural phenotype. We have previously reported attenuated prepulse inhibition (PPI) of the startle reaction in adult female rats derived...... paradigm of stressors affected the PPI response pattern in male rats. In prenatally manipulated males, the PPI response differed statistically significantly, depending on prior exposure to an episode of postnatal acute stress (blood sampling under restraint). In contrast, the PPI response in control males...... was unaffected by this postnatal experience. The present work supports the hypothesis that the maternal environment is a long-term determinant of phenotypic differences in sensitivity to stressors....

  18. 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.

  19. Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

    Science.gov (United States)

    Murphy, Margaret O; Herald, Joseph B; Wills, Caleb T; Unfried, Stanley G; Cohn, Dianne M; Loria, Analia S

    2017-02-01

    Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease. Copyright © 2017 the American Physiological Society.

  20. High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring.

    Directory of Open Access Journals (Sweden)

    Sarah J Borengasser

    Full Text Available The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosis, and lipogenic gene expression in the liver at weaning. However, the precise underlying mechanisms leading to metabolic dysregulation in the offspring remains unclear. Using a rat model of overfeeding-induced obesity, we previously demonstrated that exposure to maternal obesity from pre-conception to birth, is sufficient to program increased obesity risk in the offspring. Offspring of obese rat dams gain greater body weight and fat mass when fed high fat diet (HFD as compared to lean dam. Since, disruptions of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver, we examined the hypothesis that maternal obesity leads to perturbations of core clock components and thus energy metabolism in offspring liver. Offspring from lean and obese dams were examined at post-natal day 35, following a short (2 wk HFD challenge. Hepatic mRNA expression of circadian (CLOCK, BMAL1, REV-ERBα, CRY, PER and metabolic (PPARα, SIRT1 genes were strongly suppressed in offspring exposed to both maternal obesity and HFD. Using a mathematical model, we identified two distinct biological mechanisms that modulate PPARα mRNA expression: i decreased mRNA synthesis rates; and ii increased non-specific mRNA degradation rate. Moreover, our findings demonstrate that changes in PPARα transcription were associated with epigenomic alterations in H3K4me3 and H3K27me3 histone marks near the PPARα transcription start site. Our findings indicated that offspring from obese rat dams have detrimental alternations to circadian machinery that may contribute to impaired liver metabolism in response to HFD, specifically via reduced PPAR

  1. Assessment of female reproductive endpoints in Sprague-Dawley rats developmentally exposed to Diuron: potential ovary toxicity.

    Science.gov (United States)

    Grassi, Tony Fernando; Guerra, Marina Trevisan; Perobelli, Juliana Elaine; de Toledo, Fabíola Choqueta; da Silva, Denise Salioni; De Grava Kempinas, Wilma; Barbisan, Luís Fernando

    2011-10-01

    Diuron is widely used in agriculture but its deleterious effects on the reproductive system and mammary gland are still poorly understood. This study evaluated whether early-life-stage exposure to Diuron alters puberty onset or susceptibility to mammary carcinogenesis in female Sprague-Dawley rats. Pregnant rats received basal diet or diet containing Diuron at 500, 750, and 1,250 ppm, from gestational day 12 to the end of lactation (postnatal day 21 [PND21]). After weaning, female offspring continued receiving basal diet or diet containing Diuron until PND 51. At PND 51, female Sprague-Dawley offspring received a single dose of 50 mg/kg b.w. of 7,12-dimethylbenz(a)anthracene (DMBA) for initiation of mammary carcinogenesis. The animals were sacrificed on PND 51, 75, and 226 to 233 (week 25) for mammary gland morphology, reproductive organs and tumor analysis, respectively. There were no significant differences among groups on vaginal opening, estrous cycle, mammary morphology, or carcinogenesis. However, reductions in ovary weight and corpora lutea were observed at PND 75 in the group treated with Diuron at 1,250 ppm. The findings suggesting that Diuron exposure (1,250 ppm) may have been potentially toxic to the ovaries. © 2011 Wiley Periodicals, Inc.

  2. POMC and NPY mRNA expression during development is increased in rat offspring brain from mothers fed with a high fat diet.

    Science.gov (United States)

    Klein, Marianne Orlandini; MacKay, Harry; Edwards, Alexander; Park, Su-Bin; Kiss, Ana Carolina Inhasz; Felicio, Luciano Freitas; Abizaid, Alfonso

    2018-02-01

    Developmental programing is influenced by perinatal nutrition and it has long-lasting impacts on adult metabolism in the offspring. In particular, maternal high fat diet has been associated with increased risk of obesity and metabolic disorders during adulthood in the descendants. These effects may be due to the effects of the high fat diet on the development of the systems that regulate food intake and energy balance in the offspring hypothalamus. The arcuate nucleus (ARC) may be a particularly sensitive region to it as this nucleus contains the POMC and AgRP/NPY neurons that integrate the melanocortin system. Thus, the aim of this study was to investigate the effects of maternal high fat diet during pregnancy on the transcription factors that regulate hypothalamic development in the offspring as a potential mechanism that may result in altered neuronal expression of POMC, NPY and/or AgRP. To this end, pregnant females exposed to high fat diet (60% fat diet since day 0 of pregnancy) or standard rat chow were sacrificed on days 12, 14, 16 and 18 of gestation to obtain brains from their developing fetuses and examine the mRNA expression of transcription factors associated with the development of cells in the ARC. Results show that, while no changes in transcription factor expression between groups were observed, POMC and NPY mRNA expression were higher on embryonic day 18 in the high fat group. These results suggest that POMC and NPY expression are altered by in utero exposure to a high fat diet, but these changes in gene expression are not associated with changes in the expression of transcription factors known to determine the fate of ARC cells. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  4. 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.

  5. Toxicogenomic study in rat thymus of F1 generation offspring following maternal exposure to silver ion

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    Xiugong Gao

    2015-01-01

    Full Text Available Male and female rats (26-day-old were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc in drinking water for 10 weeks prior to and during mating. Sperm-positive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs in each dose group using a loose criterion of fold change (FC >1.5 and unadjusted p < 0.05, regardless of whether the analysis was conducted within each gender group or with both gender groups combined. No dose-dependent effect was observed on the number of DEGs. In addition, none of these genes had a false discovery rate (FDR <0.05 after correction for multiple testing. These results in combination with the observation that thymus-to-body-weight ratios were not affected and no histopathological abnormalities were identified indicate that in utero exposure to silver ions up to 26.0 mg/kg (equivalent to 40.0 mg/kg silver acetate did not have an adverse effect on the developing thymus.

  6. SWIMMING ENHANCES BONE MASS ACQUISITION IN GROWING FEMALE RATS

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    Joanne McVeigh

    2010-12-01

    Full Text Available Growing bones are most responsive to mechanical loading. We investigated bone mass acquisition patterns following a swimming or running exercise intervention of equal duration, in growing rats. We compared changes in bone mineral properties in female Sprague Dawley rats that were divided into three groups: sedentary controls (n = 10, runners (n = 8 and swimmers (n = 11. Runners and swimmers underwent a six week intervention, exercising five days per week, 30min per day. Running rats ran on an inclined treadmill at 0.33 m.s-1, while swimming rats swam in 25oC water. Dual energy X-ray absorptiometry scans measuring bone mineral content (BMC, bone mineral density (BMD and bone area at the femur, lumbar spine and whole body were recorded for all rats before and after the six week intervention. Bone and serum calcium and plasma parathyroid hormone (PTH concentrations were measured at the end of the 6 weeks. Swimming rats had greater BMC and bone area changes at the femur and lumbar spine (p < 0.05 than the running rats and a greater whole body BMC and bone area to that of control rats (p < 0.05. There were no differences in bone gain between running and sedentary control rats. There was no significant difference in serum or bone calcium or PTH concentrations between the groups of rats. A swimming intervention is able to produce greater beneficial effects on the rat skeleton than no exercise at all, suggesting that the strains associated with swimming may engender a unique mechanical load on the bone

  7. 3. Impact of altered gravity on CNS development and behavior in male and female rats

    Science.gov (United States)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

  8. Serum Trace Element Presentation in Female Wistar Rats ...

    African Journals Online (AJOL)

    Serum Trace Element Presentation in Female Wistar Rats administered with Paracetamol & Paracetamol/Methionine. AA Iyanda, FAA Adeniyi. Abstract. A number of therapeutic agents are known to alter serum trace element levels with dangerous consequences. An earlier study had demonstrated significant alteration in the ...

  9. Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring.

    Science.gov (United States)

    Paek, David S; Sakurai, Reiko; Saraswat, Aditi; Li, Yishi; Khorram, Omid; Torday, John S; Rehan, Virender K

    2015-02-01

    Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders. © The Author(s) 2014.

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

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    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

  11. 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.

  12. Pre- and/or postnatal protein restriction in rats impairs learning and motivation in male offspring.

    Science.gov (United States)

    Reyes-Castro, L A; Rodriguez, J S; Rodríguez-González, G L; Wimmer, R D; McDonald, T J; Larrea, F; Nathanielsz, P W; Zambrano, E

    2011-04-01

    Suboptimal developmental environments program offspring to lifelong health complications including affective and cognitive disorders. Little is known about the effects of suboptimal intra-uterine environments on associative learning and motivational behavior. We hypothesized that maternal isocaloric low protein diet during pregnancy and lactation would impair offspring associative learning and motivation as measured by operant conditioning and the progressive ratio task, respectively. Control mothers were fed 20% casein (C) and restricted mothers (R) 10% casein to provide four groups: CC, RR, CR, and RC (first letter pregnancy diet and second letter lactation diet), to evaluate effects of maternal diet on male offspring behavior. Impaired learning was observed during fixed ratio-1 operant conditioning in RC offspring that required more sessions to learn vs. the CC offspring (9.4±0.8 and 3.8±0.3 sessions, respectively, pmotivational effects during the progressive ratio test revealed less responding in the RR (48.1±17), CR (74.7±8.4), and RC (65.9±11.2) for positive reinforcement vs. the CC offspring (131.5±7.5, plearning and motivation behavior with the nutritional challenge in the prenatal period showing more vulnerability in offspring behavior. Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. Impact of maternal dietary exposure to endocrine-acting chemicals on progesterone receptor expression in microdissected hypothalamic medial preoptic areas of rat offspring

    International Nuclear Information System (INIS)

    Takagi, Hironori; Shibutani, Makoto; Lee, Kyoung-Youl; Masutomi, Naoya; Fujita, Haruka; Inoue, Kaoru; Mitsumori, Kunitoshi; Hirose, Masao

    2005-01-01

    We have previously examined the impact of perinatal exposure to ethinylestradiol (EE), methoxychlor (MXC), diisononyl phthalate (DINP), and genistein (GEN) in maternal diet on rat offspring, and found developmental and/or reproductive toxicity with 0.5 ppm EE, 1200 ppm MXC, and 20,000 ppm DINP. Although the toxicological profile with MXC was similar to the EE case, the population changes in pituitary hormone-producing cells totally differed between the two cases, changes being evident from 240 ppm with MXC. In the present study, to assess the impact of these agents on brain sexual differentiation, region-specific mRNA expression of estrogen receptors (ER) α and β, the progesterone receptor (PR), gonadotrophin-releasing hormone, steroid receptor coactivators (SRC)-1 and -2, and calbindin-D in microdissected hypothalamic medial preoptic areas (MPOAs) at postnatal day 10 was first analyzed in rats exposed to 0.5 ppm-EE from gestational day 15 by real-time RT-PCR. Sexually dimorphic expression of ERα and PR was noted with predominance in females and males, respectively, EE up-regulating SRC-1 in males and ERβ and PR in females. Next, we similarly examined expression changes of ERα and β, PR, and SRC-1 in animals exposed to MXC at 24, 240, and 1200 ppm, DINP at 4000 and 20,000 ppm, and GEN at 1000 ppm. MXC at 1200 ppm down- and up-regulated PR in males and females, respectively, and DINP at 20,000 ppm down-regulated PR in females, while GEN did not exert any clear effects. The results thus suggest that agents causing developmental and/or reproductive abnormalities in later life may affect hypothalamic PR expression during the exposure period in early life

  14. Long-term effects of maternal exposure to Di (2-ethylhexyl Phthalate on sperm and testicular parameters in Wistar rats offspring

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    Ahmad Ali Moazedi

    2012-01-01

    Full Text Available Background: Phthalate esters have been shown to cause reproductive toxicity in both developing and adult animals. Objective: This study was designed to assess long-term effects of maternal exposure to Di (2-ethylhexyl Phthalate (DEHP on reproductive ability of both neonatal and adult male offspring.Materials and Methods: 60 female rats randomly divided in four equal groups; vehicle control and three treatment groups that received 10, 100 and 500 mg/kg/day DEHP via gavage during gestation and lactation. At different ages after birth, the volumes of testes were measured by Cavellieri method, testes weights recorded and epididymal sperm samples were assessed for number and gross morphology of spermatozoa. Following tissue processing, seminiferous tubules diameter and germinal epithelium height evaluated with morphometric techniques.Results: Mean testis weight decreased significantly (p<0.05 in 500 mg/kg/day dose group from 28 to 150 days after birth. Significant decreases were seen in total volumes of testis in 100 (p<0.05 and 500 (p<0.01 mg/kg/day doses groups until 150 days after birth. Seminiferous tubules diameter and germinal epithelium height decreased significantly in 100 (p<0.05 and 500 (p<0.01 mg/kg/day doses groups during postnatal development. Also, mean sperm density in 100 mg/kg/day (p<0.05 and 500 mg/kg/day (p<0.01 doses groups and percent of morphologically normal sperm in highest dose group (p<0.05 decreased significantly until 150 days after birth. Conclusion: Present study showed that maternal exposure to Di (2-ethylhexyl Phthalate during gestation and lactation caused to permanent and dose-related reductions of sperm and testicular parameters in rats offspring

  15. Few long-term consequences after prolonged maternal separation in female Wistar rats.

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    Stina Lundberg

    Full Text Available Environmental factors during the early-life period are known to have long-term consequences for the adult phenotype. An intimate interplay between genes and environment shape the individual and may affect vulnerability for psychopathology in a sex-dependent manner. A rodent maternal separation model was here used to study the long-term effects of different early-life rearing conditions on adult behavior, HPA axis activity and long-term voluntary alcohol intake in female rats. Litters were subjected to 15 min (MS15 or 360 min (MS360 of daily maternal separation during postnatal day 1-21. In adulthood, the behavioral profiles were investigated using the multivariate concentric square field™ (MCSF test or examined for HPA axis reactivity by cat-odor exposure with subsequent characterization of voluntary alcohol intake and associated changes in HPA axis activity. Adult female MS360 offspring showed mostly no, or only minor, effects on behavior, HPA axis reactivity and long-term alcohol intake relative to MS15. Instead, more pronounced effects were found dependent on changes in the natural hormonal cycle or by the choice of animal supplier. However, changes were revealed in corticosterone load after long-term alcohol access, as females subjected to MS360 had higher concentrations of fecal corticosterone. The present findings are in line with and expand on previous studies on the long-term effects of maternal separation in female rats with regard to behavior, HPA axis activity and voluntary alcohol intake. It can also be a window into further studies detailing how early-life experiences interact with other risk and protective factors to impact the adult phenotype and how possible sex differences play a role.

  16. 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...

  17. 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...

  18. A Method for Recording Urethral Pressure Profiles in Female Rats.

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    Shengfei Xu

    Full Text Available Urethral pressure profile (UPP and leak-point pressure (LPP measurements as well as external urethral sphincter (EUS electromyography (EMG and videourodynamic analyses are the primary methods for evaluating urethral function in humans. However, UPP recording in female rats, a widely used animal model, is challenging due to their small body sizes. This study reports a novel method for recording UPP in female rats.Seventeen anesthetized female rats were studied. LPP data for 14 rats were included. The other 3 rats were excluded because of death or abnormal urogenital organs. UPP curves were recorded using a modified water-perfusion catheter system, with the lateral hole facing the 3-, 6-, 9-, and 12-o'clock positions in a randomized sequence. LPP, functional urethral length (FUL and maximum urethral closure pressure (MUCP were analyzed.The mean LPP was 64.39 ± 20.29 cm H2O. The mean FUL and MUCP values at the 3-, 6-, 9-, and 12-o'clock positions were 12.90 ± 1.20, 16.70 ± 1.95, 13.90 ± 2.42, and 11.60 ± 0.97 mm, respectively, and 38.70 ± 11.85, 33.90 ± 11.82, 37.40 ± 11.95, and 71.90 ± 23.01 cm H2O, respectively. The FUL at the 6-o'clock position and MUCP at the 12-o'clock position were significantly greater than those at the other 3 positions. The FUL and MUCP of repeated UPP recordings were not significantly different than those of the first recordings.UPP recording using a modified method based on a water-perfusion catheter system is feasible and replicable in female rats. It produces UPP curves that sensitively and appreciably reflect detailed pressure changes at different points within the urethra and thus provides opportunity to evaluate urethral structures, especially the urethral sphincter, in detail. These results may enhance the utility of female rat models in research of urinary sphincter mechanisms.

  19. Intravenous gestational cocaine in rats: effects on offspring development and weanling behavior.

    Science.gov (United States)

    Kunko, P M; Moyer, D; Robinson, S E

    1993-01-01

    Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of saline (SAL), via the tail vein, on gestation days 8-20. A third group was untreated (UT). Maternal weight gain was not affected by dam treatment despite slight differences in food intake. Litter characteristics (e.g., litter size, pup weight) did not differ among groups. Indices of fetal mortality were not affected by the treatments. Developmental tests, initiated on postnatal day (PND) 2, indicated slight delays in the negative geotaxic response and eye opening in cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21. Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or saline was injected prior to the tail flick test. Pups from CN dams exhibited a significant decrease in spontaneous exploratory behavior compared to both controls, and a time-dependent increase in rearing compared to pups from UT dams. The acute cocaine injection prior to placement in the open field did not alter locomotion or rearing among dam treatment groups. However, the acute cocaine injection did increase stereotypy ratings for female pups from CN dams compared to similarly treated males, and females from SAL and UT dams. No differences were observed among groups in the tail-flick test. These data suggest that the IV route of administration provides a viable method of cocaine delivery in pregnant rats, and provides further evidence of the developmental and behavioral teratogenicity of prenatal cocaine exposure.

  20. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  1. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    International Nuclear Information System (INIS)

    Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

    2012-01-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  2. Changes in the endocrine system which controls reproduction in female rats neonatally exposed to a low-dose of gamma irradiation

    International Nuclear Information System (INIS)

    Freud, A.

    1988-06-01

    Exposure of animals to high doses of ionizing radiation causes irreversible damage to the reproductive system and brings upon infertility. The results of this work indicate that neonatal exposure of female rats on day 8 of life to gamma irradiation of 6 R and 15 R causes reduction in number of offspring these rats produce when mature. The latter results from hormonal changes in the endocrine system which controls reproduction. However, one could not define one site of the hypothalamo - hypophyseal - ovarian axis which when damaged would be responsible for the radiation-induced damage to the productive system. (Author)

  3. Estimating expenditure on male and female offspring in a sexually size-dimorphic bird : A comparison of different methods

    NARCIS (Netherlands)

    Magrath, Michael J. L.; Van Lieshout, Emile; Pen, Ido; Visser, G. Henk; Komdeur, Jan

    2007-01-01

    1. The parents of sexually size-dimorphic offspring are often assumed to invest more resources producing individuals of the larger sex. A range of different methods have been employed to estimate relative expenditure on the sexes, including quantifying sex-specific offspring growth, food intake,

  4. Estimating expenditure on male and female offspring in a sexually size-dimorphic bird : A comparison of different methods

    NARCIS (Netherlands)

    Magrath, Michael J. L.; Van Lieshout, Emile; Pen, Ido; Visser, G. Henk; Komdeur, Jan

    1. The parents of sexually size-dimorphic offspring are often assumed to invest more resources producing individuals of the larger sex. A range of different methods have been employed to estimate relative expenditure on the sexes, including quantifying sex-specific offspring growth, food intake,

  5. A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

    2010-05-01

    Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

  6. Different male versus female breeding periodicity helps mitigate offspring sex ratio skews in sea turtles

    Directory of Open Access Journals (Sweden)

    Graeme Clive Hays

    2014-09-01

    Full Text Available The implications of climate change for global biodiversity may be profound with those species with little capacity for adaptation being thought to be particularly vulnerable to warming. A classic case of groups for concern are those animals exhibiting temperature-dependent sex-determination (TSD, such as sea turtles, where climate warming may produce single sex populations and hence extinction. We show that, globally, female biased hatchling sex ratios dominate sea turtle populations (exceeding 3:1 in >50% records, which, at-a-glance, reiterates concerns for extinction. However, we also demonstrate that more frequent breeding by males, empirically shown by satellite tracking 23 individuals and supported by a generalized bio-energetic life history model, generates more balanced operational sex ratios (OSRs. Hence, concerns of increasingly skewed hatchling sex ratios and reduced population viability are less acute than previously thought for sea turtles. In fact, in some scenarios skewed hatchling sex ratios in groups with TSD may be adaptive to ensure optimum OSRs.

  7. Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats.

    Science.gov (United States)

    da Silva, Flávia R M; Grassi, Tony F; Zapaterini, Joyce R; Bidinotto, Lucas T; Barbisan, Luis F

    2017-06-01

    Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy

    DEFF Research Database (Denmark)

    Armitage, James A.; Lakasing, Lorin; Taylor, Paul D.

    2005-01-01

    Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard......-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration...... weight, glomerular number or volume in OHF compared with OC, but renin and Na+,K+-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces...

  9. Factors influencing fluoxetine-induced sexual dysfunction in female rats

    Science.gov (United States)

    Adams, Sarah; Heckard, Danyeal; Hassell, James; Uphouse, Lynda

    2012-01-01

    Treatment with selective serotonin reuptake inhibitors, such as fluoxetine, produces sexual side effects with low sexual desire being the most prevalent effect in females. In few studies have preclinical models for such antidepressant-induced sexual dysfunction been fruitful. In the current manuscript, the effects of fluoxetine on multiple measures of female sexual motivation and sexual receptivity were examined. Ovariectomized, Fischer rats were primed with 10 μg estradiol benzoate and 500 μg progesterone. Partner preference, active investigation of the male, and measures of sexual behavior were examined after injection with 15 mg/kg fluoxetine. Factors (pretesting for sexual behavior, size of the test arena, non-contact time with a male) that differ among experiments designed to study antidepressant-induced female rat sexual dysfunction were studied. The male preference ratio was not affected by fluoxetine treatment but active investigation of the male was reduced; lordosis behavior was inhibited and pretesting for sexual receptivity amplified fluoxetine's inhibition; size of the testing arena or non-contact experience with the male had no effect. Regardless of test condition, when given the opportunity to escape from the male, fluoxetine-treated females displayed escape behavior. Measures of male preference and active investigation, but not lordosis behavior, appeared to be affected by fluoxetine's impact on activity. The collective data provided a behavioral profile of fluoxetine-induced sexual dysfunction. These findings reinforce the value of multiple measures when attempting to model antidepressant-induced female sexual dysfunction. PMID:22835821

  10. Decreased duration of pentobarbital-induced narcosis in immature and adult female rats prenatally exposed to cimetidine

    International Nuclear Information System (INIS)

    Donnelly, D.A.; Iba, M.M.

    1986-01-01

    The effect of prenatal cimetidine exposure (PreCM) on the duration of pentobarbital-induced narcosis (DPN) was assessed in immature (14- and 28-day old) and adult (50-60-day old) male and female rats. PreCM exposure was accomplished by treating mothers with cimetidine (CM) (20 mg/kg, ip) daily for the last two days of gestation and then (0.01% in drinking water) throughout lactation. Pregnant mothers of untreated offspring (Con) received saline. PreCM decreased DPN to 505 +/- 33 min (from 611 +/- 23 min in Con) and 393 +/- 190 min (from 686 +/- 44 min in Con) in 14-day old male and female rats, respectively. Similarly, PreCM decreased DPN to 88 +/- 15 min (from 134 +/- 3 min in Con) and 102 +/- 19 min (from 171 +/- 44 min in Con) in 28-day old male and female rats, respectively. At 21 days, PreCM did not alter DPN in either sex. At 50-60 days, however, it decreased DPN to 144 +/- 41 min (from 238 +/- 7 min in Con) in females but had no effect in males; PreCM also increased the plasma clearance of administered 14 C-pentobarbital more in females than in males. The effects of PreCM, particularly the long-term effects, were most prominent in female rats and were the opposite of those of postnatal treatment with CM. The results together with those of studies with hepatic microsomes suggest that PreCM may have resulted in the induction of hepatic drug-metabolizing enzymes during the perinatal period

  11. The effects of prenatal sound stress on the spatial learning and memory of rat's male offspring

    Directory of Open Access Journals (Sweden)

    Barzegar M

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Numerous evidences indicate that various environmental stresses during pregnancy affect physiological behavior of the offspring. This experimental study was designed to investigate the effect of noise stress during prenatal period of rats on spatial learning and memory and plasma corticostrone level in postnatal life."n"nMethods: Three groups of pregnant rats were given daily noise stress with durations of two and/ or four hours in last week of pregnancy period. The fourth group was left unstressed. The male offspring from the unstressed and different stressed groups were assigned as controls and stressed groups. The animals were introduced to a spatial task in Morris water maze 4 trials/day for five consecutive days. The probe test was performed on the 5th day of the experiment. The delay in findings and the distance passed to locate the target platform were assessed as the spatial learning. "n"nResults: Our results showed that prenatal exposure to noise stress for two and/ or four hours a day, leads to impaired acquisition of spatial learning in the postnatal animals. The plasma level of corticostrone in the two stressed groups of rats markedly matched with their behavioral function. Prenatal exposure to 1- hour noise stress revealed no effects on the offsprings' behavior and plasma corticostrone level."n"nConclusion: Based on our study results, it seems that applied range of stress which is executed through the noise stress could increase the plasma corticostrone level and

  12. 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.

  13. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    Science.gov (United States)

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  14. Fructose intake during gestation and lactation differentially affects the expression of hippocampal neurosteroidogenic enzymes in rat offspring.

    Science.gov (United States)

    Mizuno, Genki; Munetsuna, Eiji; Yamada, Hiroya; Ando, Yoshitaka; Yamazaki, Mirai; Murase, Yuri; Kondo, Kanako; Ishikawa, Hiroaki; Teradaira, Ryoji; Suzuki, Koji; Ohashi, Koji

    2017-02-01

    Neurosteroids, steroidal hormones synthesized de novo from cholesterol within the brain, stimulate hippocampal functions such as neuron protection and synapse formation. Previously, we examined the effect of maternal fructose on the transcriptional regulation of neurosteroidogenic enzymes. We found that the mRNA expression level of the steroidogenic acute regulatory protein (StAR), peripheral benzodiazepine receptor (PBR), cytochrome P450(11β), 11β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD was altered. However, we could not determine whether maternal fructose intake played a role in the gestation or lactation period because the dam rats were fed fructose solution during both periods. Thus, in this study, we analyzed the hippocampi of the offspring of dams fed fructose during the gestation or lactation period. Maternal fructose consumption during either the gestation or lactation period did not affect the mRNA levels of StAR, P450(17α), 11β-HSD-2, and 17β-HSD-1. PBR expression was down-regulated, even when rats consumed fructose during the lactation period only, while fructose consumption during gestation tended to activate the expression of P450(11β)-2. We found that maternal fructose intake during gestation and lactation differentially affected the expression of hippocampal neurosteroidogenic enzymes in the offspring.

  15. Disposition of perfluorodecanoic acid in male and female rats

    International Nuclear Information System (INIS)

    Vanden Heuvel, J.P.; Kuslikis, B.I.; Van Rafelghem, M.J.; Peterson, R.E.

    1991-01-01

    The elimination, tissue distribution, and metabolism of [1-14C]PFDA were examined in male and female rats for 28 days after a single ip dose (9.4 mumol/kg, 5 mg/kg). A sex difference in the fecal elimination of perfluorodecanoic acid (PFDA) was observed with 51 and 24% of the administered 14C being recovered in the feces of male and female rats, respectively, by 28 days post-treatment. The cumulative excretion of PFDA-derived 14C in the urine in 28 days was less than 5% of the administered dose in both sexes. The sex-related difference in the rate of fecal elimination resulted in the observed difference in whole body elimination t1/2 of PFDA in males (t1/2 = 23 days) and females (t1/2 = 45 days). The liver contained the highest concentration of PFDA-derived 14C in both males and females, followed by the plasma and kidneys. The heart, fat pads, testes, and gastrocnemius muscle of males, and the ovaries of females contained much lower concentrations of PFDA. The reason for the high percentage of the ip dose of [1-14C]PFDA in the liver (53% males and 41% females, 2 hr post-treatment) was further examined using an in situ nonrecirculating liver perfusion technique. It was shown that approximately 25% of the [14C]PFDA in the perfusate was extracted by the liver in a single pass. The basis for the sex difference in fecal elimination of PFDA does not appear to be due to a sex difference in biliary excretion. In a 6-hr period, male and female rats with kidneys ligated eliminated essentially the same percentage dose of [14C]PFDA into bile. We had hypothesized that the persistence of PFDA in rats was due to formation of a PFDA-containing lipids. However, no evidence that PFDA is conjugated to form persistent hybrid lipids was obtained, nor were polar metabolites of PFDA detected in urine or bile

  16. Effects of thiamine deficiency on food intake and body weight increment in adult female and growing rats.

    Science.gov (United States)

    Bâ, Abdoulaye

    2012-09-01

    The present study compared the effects of thiamine (vitamin B1) deficiency (TD) on the patterns of food intake and body weight in adult female and neonatal Wistar rats. The adults weighed 250-270 g at the start and were fed for 60 days either with a synthetic TD diet (211 B1) or with the same synthetic diet+thiamine (210 B1). TD led to a marked reduction in food intake and the body weight set point, both recovering rapidly to their initial level in only 3 days after dietetic reversion. The effects of TD in developing rats were evaluated by subjecting pregnant rats to thiamine restriction during different time windows: prenatal (3 days before mating to parturition); perinatal (7 days after mating to the 10th postnatal day); and postnatal (from parturition to weaning). The effect of TD on the occurrence of low birth weight and ponderal growth retardation was examined from postnatal days 1 to 45. Only perinatal TD significantly decreased birth weight relative to untreated or pair-fed controls. Moreover, compared with the control treatments, ponderal growth retardation was not induced by prenatal TD, whereas induction of TD from perinatal into postnatal periods did cause ponderal growth retardation, with long-lasting effects persisting in adulthood. The results suggest a major physiological role of thiamine in the homeostasis of body weight programming, increment, and set point regulation in both offspring and adult female rats.

  17. Effects of Thyroid Dysfunction on Reproductive Hormones in Female Rats.

    Science.gov (United States)

    Liu, Juan; Guo, Meng; Hu, Xusong; Weng, Xuechun; Tian, Ye; Xu, Kaili; Heng, Dai; Liu, Wenbo; Ding, Yu; Yang, Yanzhou; Zhang, Cheng

    2018-05-10

    Thyroid hormones (THs) play a critical role in the development of ovarian cells. Although the effects of THs on female reproduction are of great interest, the mechanism remains unclear. We investigated the effects of TH dysregulation on reproductive hormones in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyper-thyroidism, respectively, and the reproductive hormone profiles were analyzed by radioimmunoassay. Ovarian histology was evaluated with H&E staining, and gene protein level or mRNA content was analyzed by western blotting or RT-PCR. The serum levels of gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in both rat models were significantly decreased on day 21, although there were no significant changes at earlier time points. There were no significant differences in luteinizing hormone (LH) or progesterone levels between the treatment and the control groups. Both PTU and L-thyroxine treatments downregulated estradiol concentrations; however, the serum testosterone level was increased only in hypothyroid rats at day 21. In addition, the expression levels of FSH receptor, cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic acute regulatory protein were decreased in both rat models. Moreover, the onset of puberty was significantly delayed in the hypothyroid group. These results provide evidence that TH dysregulation alters reproductive hormone profiles, and that the initiation of the estrous cycle is postponed in hypothyroidism.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Semisterility in F/sub 1/ male progeny of female rats exposed to fractional 300 R X-rays and the effect of cysteamine or cystamine retreatment

    Energy Technology Data Exchange (ETDEWEB)

    Baev, I; Bajrakova, A [Nauchno-Izsledovatelski Inst. po Radiologiya i Radiatsionna Khigiena, Sofia (Bulgaria)

    1975-01-01

    Female rats are fractionally irradiated with a total dose of 800 R (on 20 consecutive days x 40 R) with or without chemical protection. Radioprotectors - cysteamine or cystamine - are administered in doses of 5 mg per rat intraperitoneally (cysteamine), resp. 20 mg per rat orally (cystamine) prior to each irradiation procedure. The fertility of the male offsprings born to irradiated mothers crossed with intact males six months after treatment is studied. For that purpose, each male of this progeny have been coupled with five intact females and the embryonic death rate in the second generation is checked up. The percentage of semisterile animals is high. Preliminary treatment of the mother with cysteamine or cystamine resulted in a more severe injury than the one following protection-free irradiation.

  20. Semisterility in F1 male progeny of female rats exposed to fractional 300 R X-rays and the effect of cysteamine or cystamine retreatment

    International Nuclear Information System (INIS)

    Baev, I.; Bajrakova, A.

    1975-01-01

    Female rats are fractionally irradiated with a total dose of 800 r (on 20 consecutive days x 40 r) with or without chemical protection. Radioprotectors - cysteamine or cystamine - are administered in doses of 5 mg per rat intraperitoneally (cysteamine), resp. 20 mg per rat orally (cystamine) prior to each irradiation procedure. The fertility of the male offsprings born to irradiated mothers crossed with intact males six months after treatment is studied. For that purpose, each male of this progeny have been coupled with five intact females and the embryonic death rate in the second generation is checked up. The percentage of semisterile animals is high. Preliminary treatment of the mother with cysteamine or cystamine resulted in a more severe injury than the one following protection-free irradiation. (Ch.K.)

  1. Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats

    NARCIS (Netherlands)

    Heinsbroek, A. C. M.; van Dijk, G.

    Introduction: Excessive gestational body weight gain of mothers may predispose offspring towards obesity and metabolic derangements. It is difficult to discern the effects of maternal obesogenic factors-such as diet and/or thrifty genetic predisposition-from gestational weight gain per se. Methods:

  2. 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.

  3. Exposure to a highly caloric palatable diet during pregestational and gestational periods affects hypothalamic and hippocampal endocannabinoid levels at birth and induces adiposity and anxiety-like behaviors in male rat offspring

    Directory of Open Access Journals (Sweden)

    Maria Teresa eRamírez-López

    2016-01-01

    Full Text Available Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigated. Exposure to a palatable diet resulted in low weight offspring who exhibited low hypothalamic contents of arachidonic acid and the two major endocannabinoids (anandamide and 2-arachidonoylglycerol at birth. Palmitoylethanolamide, but not oleoylethanolamide, also decreased. Additionally, pups from palatable diet-fed dams displayed lower levels of anandamide and palmitoylethanolamide in the hippocampus. The low-weight male offspring, born from palatable diet exposed mothers, gained less weight during lactation and, although they recovered weight during the post-weaning period, they developed abdominal adiposity in adulthood. These animals exhibited anxiety-like behavior in the elevated plus-maze and open field test and a low preference for a chocolate diet in a food preference test, indicating that maternal exposure to a hypercaloric diet induces long-term behavioral alterations in male offspring. These results suggest that maternal diet alterations in the function of the endogenous cannabinoid system can mediate the observed phenotype of the offspring, since both hypothalamic and hippocampal endocannabinoids regulate feeding, metabolic adaptions to caloric diets, learning, memory and emotions.

  4. Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

    Science.gov (United States)

    Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

    2014-05-01

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a

  5. Female offspring desertion and male-only care increase with natural and experimental increase in food abundance

    OpenAIRE

    Eldegard, Katrine; Sonerud, Geir A.

    2009-01-01

    In species with biparental care, one parent may escape the costs of parental care by deserting and leaving the partner to care for the offspring alone. A number of theoretical papers have suggested a link between uniparental offspring desertion and ecological factors, but empirical evidence is scarce. We investigated the relationship between uniparental desertion and food abundance in a natural population of Tengmalm's owl Aegolius funereus, both by means of a 5-year observational study and a...

  6. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring.

    Directory of Open Access Journals (Sweden)

    Linglin Xie

    Full Text Available Adipose tissue macrophages (ATM are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. The study aims to answer whether maternal undernutrition by protein restriction affects the ATM M1 or M2 phenotype under postnatal high fat diet in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein diet followed by a postnatal high fat energy diet (HE, 45% fat or low fat normal energy diet (NE, 10% fat for 12 weeks, we investigated the effects of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response in adipose tissue. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. In offspring fed HE, LP offspring had a lower percentage of CD11c+CD206+ ATMs, whose abundancy was correlated with the size of the adipocytes. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1β transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6.

  7. Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.

    Science.gov (United States)

    Pyter, Leah M; El Mouatassim Bih, Sarah; Sattar, Husain; Prendergast, Brian J

    2014-03-13

    Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250μg/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1β], CD11b, IκBα, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il-1β and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1β and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, IκBα was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Participation of locus coeruleus in breathing control in female rats.

    Science.gov (United States)

    de Carvalho, Débora; Patrone, Luis Gustavo A; Marques, Danuzia A; Vicente, Mariane C; Szawka, Raphael E; Anselmo-Franci, Janete A; Bícego, Kênia C; Gargaglioni, Luciane H

    2017-11-01

    Several evidences indicate that the locus coeruleus (LC) is involved in central chemoreception responding to CO 2 /pH and displaying a high percentage of chemosensitive neurons (>80%). However, there are no studies about the LC-mediated hypercapnic ventilation performed in females. Therefore, we assessed the role of noradrenergic LC neurons in non-ovariectomized (NOVX), ovariectomized (OVX) and estradiol (E2)-treated ovariectomized (OVX+E2) rats in respiratory response to hypercapnia, using a 6-hydroxydopamine (6-OHDA) - lesion model. A reduction in the number of tyrosine hydroxylase (TH) immunoreactive neurons (51-90% in 3 animals of NOVX group, 20-42% of lesion in 5 animals of NOVX females, 61.3% for OVX and 62.6% for OVX+E2 group) was observed seven days after microinjection of 6-OHDA in the LC. The chemical lesion of the LC resulted in decreased respiratory frequency under normocapnic conditions in OVX and OVX+E2 group. Hypercapnia increased ventilation in all groups as consequence of increases in respiratory frequency (fR) and tidal volume (V T ). Nevertheless, the hypercapnic ventilatory response was significantly decreased in 6-OHDA-NOVX>50% rats compared with SHAM-NOVX group and with females that had 20-42% of LC lesion. In OVX and OVX+E2 lesioned groups, no difference in CO 2 ventilatory response was observed when compared to SHAM-OVX and SHAM-OVX+E2 groups, respectively. Neither basal body temperature (Tb) nor Tb reduction in response to hypercapnia were affected by E2 treatment, ovariectomy or LC lesion. Thus, our data show that LC noradrenergic neurons seem to exert an excitatory role on the hypercapnic ventilatory response in female rats, as evidenced by the results in NOVX animals with LC lesioned more than 50%; however, this modulation is not observed in OVX and OVX+E2 rats. In addition, LC noradrenergic neurons of OVX females seem to provide a tonic excitatory drive to maintain breathing frequency in normocapnia, and this response may not to be

  9. Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre-gestation or in gestation.

    Science.gov (United States)

    Rodriguez, J S; Rodríguez-González, G L; Reyes-Castro, L A; Ibáñez, C; Ramírez, A; Chavira, R; Larrea, F; Nathanielsz, P W; Zambrano, E

    2012-04-01

    We studied the effects of maternal high fat diet (HFD, 25% calories from fat administered before and during pregnancy and lactation) and dietary intervention (switching dams from HFD to control diet) at different periconceptional periods on male offspring anxiety related behavior, exploration, learning, and motivation. From weaning at postnatal day (PND) 21, female subjects produced to be the mothers in the study received either control diet (CTR - 5% calories from fat), HFD through pregnancy and lactation (MO), HFD during PNDs 21-90 followed by CTR diet (pre-gestation (PG) intervention) or HFD from PND 21 to 120 followed by CTR diet (gestation and lactation (G) intervention) and bred at PND 120. At 19 days of gestation maternal serum corticosterone was increased in MO and the PG and G dams showed partial recovery with intermediate levels. In offspring, no effects were found in the elevated plus maze test. In the open field test, MO and G offspring showed increase zone entries, displaying less thigmotaxis; PG offspring showed partial recuperation of this behavior. During initial operant conditioning MO, PG and G offspring displayed decreased approach behavior with subsequent learning impairment during the acquisition of FR-1 and FR-5 operant conditioning for sucrose reinforcement. Motivation during the progressive ratio test increased in MO offspring; PG and G intervention recuperated this behavior. We conclude that dietary intervention can reverse negative effects of maternal HFD and offspring outcomes are potentially due to elevated maternal corticosterone. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

  10. Sex ratio of the offspring of Sprague-Dawley rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero and lactationally in a three-generation study

    International Nuclear Information System (INIS)

    Rowlands, J.C.; Budinsky, R.A.; Aylward, L.L.; Faqi, A.S.; Carney, E.W.

    2006-01-01

    Reports of a decreased male/female sex ratio in children born to males exposed to TCDD in Seveso, Italy, at a young age have sparked examinations of this endpoint in other populations exposed to TCDD or related compounds. Overall, the male/female sex ratio results reported in these studies, with slightly different age-exposed male populations, have shown mixed results. Experimental studies of the effects of in utero exposure to TCDD in laboratory animals have reported no effect on the f 1 sex ratio and mixed results for the sex ratio of the f 2 generation. In order to better understand the potential effects of TCDD on second generation sex ratio, we retrieved archived data from a comprehensive three-generation feeding study of TCDD in rats that was conducted and published in the 1970s, but which did not publish data on sex ratio of the offspring [Murray, F.J., Smith, F.A., Nitschke, K.D., Humiston, C.G., Kociba, R.J., Schwetz, B.A., 1979. Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. Toxicol. Appl. Pharmacol. 50, 241-252]. A re-examination of the original Murray et al. data found no statistically significant treatment-related changes in postnatal day 1 sex ratio in any generation of treated animals, consistent with one other relatively large study reporting on this endpoint. We discuss mechanistic data underlying a potential effect of TCDD on this endpoint. We conclude that the inconsistency in findings on sex ratio of the offspring of male rats exposed to TCDD in utero is likely due to random variation associated with a relatively small sample size, although differences between studies in strain of rat, dose regimen, and day of ascertainment of sex ratio cannot be ruled out

  11. Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

    Science.gov (United States)

    Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

    2016-01-01

    Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

  12. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

    Science.gov (United States)

    Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

    2015-02-01

    Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

  13. Epidermal growth factor and lung development in the offspring of the diabetic rat

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    2000-01-01

    Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining...

  14. Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

    Science.gov (United States)

    Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

    2016-01-01

    Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

    Science.gov (United States)

    Petropoulos, Sophie; Guillemin, Claire; Ergaz, Zivanit; Dimov, Sergiy; Suderman, Matthew; Weinstein-Fudim, Liza; Ornoy, Asher; Szyf, Moshe

    2015-06-01

    Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

  17. Juvenile female rats, but not male rats, show renewal, reinstatement, and spontaneous recovery following extinction of conditioned fear.

    Science.gov (United States)

    Park, Chun Hui J; Ganella, Despina E; Kim, Jee Hyun

    2017-12-01

    Anxiety disorders emerge early, and girls are significantly more likely to develop anxiety compared to boys. However, sex differences in fear during development are poorly understood. Therefore, we investigated juvenile male and female rats in the relapse behaviors following extinction of conditioned fear. In all experiments, 18-d-old rats first received three white-noise-footshock pairings on day 1. On day 2, extinction involved 60 white-noise alone trials. In experiment 1, we examined renewal by testing the rats in either the same or different context as extinction on day 3. Male rats did not show renewal, however, female rats showed renewal. Experiment 2 investigated reinstatement by giving rats either a mild reminder footshock or context exposure on day 3. When tested the next day, male rats did not show reinstatement, whereas female rats showed reinstatement. Experiment 3 investigated spontaneous recovery by testing the rats either 1 or 5 d following extinction. Male rats did not show any spontaneous recovery whereas female rats did. Taken together, fear regulation appear to be different in males versus females from early in development, which may explain why girls are more prone to suffer from anxiety disorders compared to boys. © 2017 Park et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie

    2013-01-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gest...

  19. 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...

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

    NARCIS (Netherlands)

    Boulle, F.; Pawluski, J.L.; Homberg, J.R.; Machiels, B.; Kroeze, Y.; Kumar, N.; Steinbusch, H.W.; Kenis, G.; Hove, D.L. van den

    2016-01-01

    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

  1. The role of social environment on parental care: offspring benefit more from the presence of female than male helpers

    NARCIS (Netherlands)

    Brouwer, L.; Van de Pol, M.; Cockburn, A.

    2014-01-01

    1.Investment in offspring depends on the costs and benefits to the carer, which can vary with sex and social status. Investment also depends on the effort of others by allowing for compensation (load-lightening), with biparental care studies showing that this depends on the state and type of the

  2. Offspring Protection

    Directory of Open Access Journals (Sweden)

    Eric T. Steiner

    2016-08-01

    Full Text Available Parental aggression, that is, offspring protection aggression, can be viewed as a type of parental investment. Most mammalian males do not exhibit parental investment and therefore exhibit little, if any, parental aggression. Men demonstrate parental investment, and are typically more physically aggressive than women, but parental physical aggression in humans has been largely unexplored. The current study examined potential sex differences in estimates of parental physical aggression involving hypothetical situations, while controlling for general physical aggression. A self-report measure was administered to 217 students from a western U.S. university (55 male nonparents, 50 female nonparents, 54 fathers, and 58 mothers. Male nonparents reported higher parental physical aggression than female nonparents, but there was no difference between mothers and fathers. The results are interpreted in light of ancestral effects of sexual selection and proximal effects of sex differences in testosterone, risk taking, and fear aversion.

  3. Tributyltin impairs the reproductive cycle in female rats.

    Science.gov (United States)

    Lang Podratz, Priscila; Delgado Filho, Vicente Sathler; Lopes, Pedro Francisco Iguatemy; Cavati Sena, Gabriela; Matsumoto, Silvia Tamie; Samoto, Vivian Yochiko; Takiya, Christina Maeda; de Castro Miguel, Emilio; Silva, Ian Victor; Graceli, Jones Bernardes

    2012-01-01

    Triorganotins are environmental contaminants, commonly used in antifouling agents for boats, that bioaccumulate and thus are found in mammals and humans due to ingestion of contaminated seafood diets. The importance of triorganotins as environmental endocrine disruptors and consequent reproductive toxicity in different animal models is well known; however, the adverse effects on reproductive cycle are less well understood. The potential reproductive toxicity of tributyltin (TBT) on regular reproductive cycling of female rats was examined. Wistar female rats (12 wk old, weighing approximately 230 g) were divided into two groups: control (vehicle, ethanol 0.4%) and tributyltin (100 ng/kg/d, 7 d/wk, for 16 d by gavage). Tributyltin significantly decreased the cycle regularity (%), duration of the reproductive cycle, the proestrus and diestrus phases, and number of epithelial cell in proestrus phase. TBT also increased the duration of metestrus and the number of cornified cells in this phase. Ovary weight and serum 17β-estradiol levels decreased markedly, accompanied by a significant increase in progesterone levels. Histological analysis showed apoptotic cells in corpus luteum and granulosa cells layer, with cystic follicles after TBT exposure. Tributyltin also elevated number of atretic follicles and corpoa lutea. The micronucleus (MN) test, using Chinese hamster ovary cells, demonstrated a concentration-dependent mutagenic effect of TBT, and at 2.0 × 10(-2)ng/ml most of the cells were nonviable. The toxic potential of TBT over the reproductive cycle may be attributed to changes found in the ovarian weight, unbalanced levels of sexual female hormones, and number of ovarian follicles and corpora lutea.

  4. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

    Science.gov (United States)

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

    2016-04-01

    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 protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. © 2016 John Wiley & Sons Australia, Ltd.

  5. Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring.

    Directory of Open Access Journals (Sweden)

    DaLiao Xiao

    Full Text Available Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

  6. Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

    Science.gov (United States)

    Cho, Clara E; Pannia, Emanuela; Huot, Pedro S P; Sánchez-Hernández, Diana; Kubant, Ruslan; Dodington, David W; Ward, Wendy E; Bazinet, Richard P; Anderson, G Harvey

    2015-03-01

    High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms. Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction. Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Experimental comparison of the reproductive outcomes and early development of the offspring of rats given five common types of drinking water.

    Directory of Open Access Journals (Sweden)

    Hui Zeng

    Full Text Available Tap water (unfiltered, filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague-Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI and offspring's learning and memory abilities (OLMA; the lowest offspring survival rate was found in the purified water group; and the highest OLMA were found in the filtered tap water group. Thus, the best reproductive and offspring early developmental outcomes were found in the group that drank filtered tap water, which had the lowest levels of pollutants and the richest minerals. Therefore, thoroughly removing toxic contaminants and retaining the beneficial minerals in drinking water may be important for both pregnant women and children, and the best way to treat water may be with granular activated carbon and ion exchange by copper zinc alloy.

  8. Experimental comparison of the reproductive outcomes and early development of the offspring of rats given five common types of drinking water.

    Science.gov (United States)

    Zeng, Hui; Chen, Ji-an; Liu, Lin; Wang, Da-hua; Fu, Wen-juan; Wang, Ling-qiao; Luo, Jiao-hua; Zhang, Liang; Tan, Yao; Qiu, Zhi-qun; Huang, Yu-jing; Shu, Wei-qun

    2014-01-01

    Tap water (unfiltered), filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water) are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients) of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague-Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI) and offspring's learning and memory abilities (OLMA); the lowest offspring survival rate was found in the purified water group; and the highest OLMA were found in the filtered tap water group. Thus, the best reproductive and offspring early developmental outcomes were found in the group that drank filtered tap water, which had the lowest levels of pollutants and the richest minerals. Therefore, thoroughly removing toxic contaminants and retaining the beneficial minerals in drinking water may be important for both pregnant women and children, and the best way to treat water may be with granular activated carbon and ion exchange by copper zinc alloy.

  9. Experimental Comparison of the Reproductive Outcomes and Early Development of the Offspring of Rats Given Five Common Types of Drinking Water

    Science.gov (United States)

    Zeng, Hui; Shu, Wei-qun; Chen, Ji-an; Liu, Lin; Wang, Da-hua; Fu, Wen-juan; Wang, Ling-qiao; Luo, Jiao-hua; Zhang, Liang; Tan, Yao; Qiu, Zhi-qun; Huang, Yu-jing

    2014-01-01

    Tap water (unfiltered), filtered tap water and processed bottled water (purified water, artificial mineralized water, or natural water) are now the five most widely consumed types of drinking water in China. However, the constituents (organic chemicals and inorganic ingredients) of the five waters differ, which may cause them to have different long-term health effects on those who drink them, especially sensitive children. In order to determine which type of water among the five waters is the most beneficial regarding reproductive outcomes and the developmental behaviors of offspring, two generations of Sprague–Dawley rats were given these five waters separately, and their reproductive outcomes and the developmental behaviors of their offspring were observed and compared. The results showed that the unfiltered tap water group had the lowest values for the maternal gestation index (MGI) and offspring's learning and memory abilities (OLMA); the lowest offspring survival rate was found in the purified water group; and the highest OLMA were found in the filtered tap water group. Thus, the best reproductive and offspring early developmental outcomes were found in the group that drank filtered tap water, which had the lowest levels of pollutants and the richest minerals. Therefore, thoroughly removing toxic contaminants and retaining the beneficial minerals in drinking water may be important for both pregnant women and children, and the best way to treat water may be with granular activated carbon and ion exchange by copper zinc alloy. PMID:25279561

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

    Science.gov (United States)

    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.

  11. Chronic high-fat diet in fathers programs ß-cell dysfunction in female rat offspring

    DEFF Research Database (Denmark)

    Ng, Sheau-Fang; Lin, Ruby C Y; Laybutt, D Ross

    2010-01-01

    The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced ...

  12. Exposure to the widely used fungicide Mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Nellemann, Christine Lydia

    2011-01-01

    The widely used fungicide Mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead...... to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal Mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100 or 150 mg Mancozeb/kg bw/day by gavage...... offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams, and was therefore reduced to 100 mg/kg bw/day in mid study. T4 levels showed a dose-dependent and significant decreased in dams from all three dose groups on GD 15, whereas offspring T4 levels, thyroid weights and histology were...

  13. Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.

    Directory of Open Access Journals (Sweden)

    Moogeh Baharnoori

    Full Text Available Epidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS model of immune activation in rats, the offspring exhibit significant impairments in behaviors mediated by central dopamine (DA system. This study aimed to examine the temporal and regional pattern of postnatal DA development in the male offspring of pregnant Sprague-Dawley rats administered with 100 µg/kg LPS or saline at gestational days 15/16. Using ligand autoradiography, D1 and D2 dopamine receptors (D1R, D2R and dopamine transporter (DAT binding levels were measured in the prefrontal cortex (PFC and sub cortical regions (dorsal striatum and nucleus accumbens core and shell at pre pubertal (P35 and post pubertal ages (P60. We found a significant decrease in D2R ligand [(3H] YM-90151-2 binding in the medial PFC (mPFC in prenatal LPS-treated animals at P35 and P60 compared to respective saline groups. The decrease in D2R levels was not observed in the striatum or accumbens of maternal LPS-treated animals. No significant changes were observed in [(3H] SCH23390 binding to D1R. However, the level of [(125I] RTI-121 binding to DAT was selectively reduced in the nucleus accumbens core and shell at P35 in the prenatal LPS group. Immunohistochemical analysis showed that number of D2R immunopositive cells in infralimbic/prelimbic (IL/PL part of mPFC was significantly reduced in the LPS group at P60. Prenatal LPS treatment did not significantly affect either the total number of mature neurons or parvalbumin (PV-immunopositive interneurons in this region. However the number of PV and D2R co-labeled neurons was significantly reduced in the IL/PL subregion of PFC of LPS treated animals. Our data suggests D2R deficit in the PFC and PV interneurons may be relevant to understanding mechanisms of cortical dysfunctions described in prenatal infection

  14. Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl phthalate and genistein

    Directory of Open Access Journals (Sweden)

    Lian-Dong Zhang

    2013-01-01

    Full Text Available Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl phthalate (DEHP and genistein (GEN during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday. The outcomes studied were general morphometry (weight, AGD, testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday, GEN(50mg/kg bwday or GEN(400mg/kg bwday alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday. When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP

  15. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring

    Science.gov (United States)

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers’ oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris. PMID:26928288

  16. High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring

    International Nuclear Information System (INIS)

    Bal, Chandrasekhar; Kumar, Ajay; Tripathi, Madhavi; Chandrashekar, Narayana; Phom, Hentok; Murali, Nadig R.; Chandra, Prem; Pant, Gauri S.

    2005-01-01

    Background: We tried to evaluate the female fertility and genetic risk to the offspring from the exposure to high-dose 131 I by assessing the pregnancy outcomes and health status of the children of female patients with differentiated thyroid cancer who had received therapeutic doses of 131 I. Materials and Methods: From 1967 to 2002, a total of 1,282 women had been treated with 131 I. Of these patients, 692 (54%) were in the reproductive age group (18-45 years). Forty women had a total of 50 pregnancies after high-dose 131 I. Age at presentation ranged from 16 to 36 years (mean, 23 ± 4 years). Histopathology was papillary thyroid cancer in 32 cases and follicular thyroid cancer in 8 cases. Results: Single high-dose therapy was given in 30 cases, 2 doses were given in 7 cases, 3 doses were given in 2 cases, and four doses were given in 1 case in which lung metastases had occurred. In 37 patients (92%), disease was successfully ablated before pregnancy. Ovarian absorbed-radiation dose calculated by the MIRD method ranged from 3.5 to 60 cGy (mean, 12 ± 11 cGy). The interval between 131 I therapy and pregnancy varied from 7 to 120 months (37.4 ± 28.2 months). Three spontaneous abortions occurred in 2 women. Forty-seven babies (20 females and 27 males) were born. Forty-four babies were healthy with normal birth weight and normal developmental milestones. Twenty women delivered their first baby after 131 I therapy. The youngest child in our series is 11 months of age, and the oldest is 8.5 years of age. Conclusions: Female fertility is not affected by high-dose radioiodine treatment, and the therapy does not appear to be associated with any genetic risks to the offspring

  17. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    Directory of Open Access Journals (Sweden)

    Desislava Abadjieva

    Full Text Available Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP 15 and growth differentiation factor (GDF 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR. The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  18. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    Science.gov (United States)

    Abadjieva, Desislava; Kistanova, Elena

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  19. Effect of Diabetes on Circulating Pancreatic Hormones in Pregnant Rats and Their Offspring

    DEFF Research Database (Denmark)

    Iessi, I L; Sinzato, Y K; Gallego, F Q

    2016-01-01

    into: control (C); mildly diabetic (MD); and severely diabetic (SD). The rats were mated and distributed into 2 subgroups: euthanasia at day 21 of pregnancy and at day 10 postpartum. Both MD and SD dams showed impaired oral glucose tolerance. SD dams had lower body weight and insulin levels compared...

  20. Influence of maternal dietary n-3 fatty acids on breast milk and liver lipids of rat dams and offspring - a preliminary study

    DEFF Research Database (Denmark)

    Hartvigsen, M.S.; Mu, Huiling; Høy, Carl-Erik

    2003-01-01

    The impact of triacylglycerol (TAG) structure and level of n-3 fatty acids on the fatty acid profile of total breast milk lipids and total liver phospholipids (PL) of dams and offspring (1, 3 and 13 weeks of age), when administered during development, was examined. Pregnant rats were fed experime......The impact of triacylglycerol (TAG) structure and level of n-3 fatty acids on the fatty acid profile of total breast milk lipids and total liver phospholipids (PL) of dams and offspring (1, 3 and 13 weeks of age), when administered during development, was examined. Pregnant rats were fed...... experimental diets from the 8(th) day of pregnancy throughout lactation. After weaning and until 13 weeks of age, the offspring were fed the same diet as their dams. The experimental diets contained either a specific structured oil, linseed oil or fish oil. In the specific structured oil, a-linolenic acid (18...... fatty acids. Samples from three animals in each group were analyzed. The highest level of 22:6n-3 in the breast milk was obtained with diets containing this fatty acid itself. The fatty acid profile of rat dam liver PL was very different from the milk lipids indicating that the maternal dietary fats...

  1. Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid composition in rat offspring.

    Science.gov (United States)

    Toop, Carla R; Muhlhausler, Beverly S; O'Dea, Kerin; Gentili, Sheridan

    2017-07-01

    Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes. Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring. Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning. Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet. Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation. Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and

  2. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

  3. Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway.

    Science.gov (United States)

    Zhong, Liang; Luo, Foquan; Zhao, Weilu; Feng, Yunlin; Wu, Liuqin; Lin, Jiamei; Liu, Tianyin; Wang, Shengqiang; You, Xuexue; Zhang, Wei

    2016-10-01

    The brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) (BDNF-TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF-TrkB signalling pathway is involved in propofol-induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real-time PCR (RT-PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated-TrkB (phospho-TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho-TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) reversed all of the observed changes. Treatment with 7,8-DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF-TrkB signalling pathway. The TrkB agonist 7,8-DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular

  4. Wild-type offspring of heterozygous prolactin receptor-null female mice have maladaptive β-cell responses during pregnancy.

    Science.gov (United States)

    Huang, Carol

    2013-03-01

    Abstract  β-Cell mass increases during pregnancy in adaptation to the insulin resistance of pregnancy. This increase is accompanied by an increase in β-cell proliferation, a process that requires intact prolactin receptor (Prlr) signalling. Previously, it was found that during pregnancy, heterozygous prolactin receptor-null (Prlr(+/-)) mice had lower number of β-cells, lower serum insulin and higher blood glucose levels than wild-type (Prlr(+/+)) mice. An unexpected observation was that the glucose homeostasis of the experimental mouse depends on the genotype of her mother, such that within the Prlr(+/+) group, the Prlr(+/+) offspring derived from Prlr(+/+) mothers (Prlr(+/+(+/+))) had higher β-cell mass and lower blood glucose than those derived from Prlr(+/-) mothers (Prlr(+/+(+/-))). Pathways that are known to regulate β-cell proliferation during pregnancy include insulin receptor substrate-2, Akt, menin, the serotonin synthetic enzyme tryptophan hydroxylase-1, Forkhead box M1 and Forkhead box D3. The aim of the present study was to determine whether dysregulation in these signalling molecules in the islets could explain the maternal effect on the phenotype of the offspring. It was found that the pregnancy-induced increases in insulin receptor substrate-2 and Akt expression in the islets were attenuated in the Prlr(+/+(+/-)) mice in comparison to the Prlr(+/+(+/+)) mice. The expression of Forkhead box D3, which plays a permissive role for β-cell proliferation during pregnancy, was also lower in the Prlr(+/+(+/-)) mice. In contrast, the pregnancy-induced increases in phospho-Jak2, tryptophan hydroxylase-1 and FoxM1, as well as the pregnancy-associated reduction in menin expression, were comparable between the two groups. There was also no difference in expression levels of genes that regulate insulin synthesis and secretion (i.e. glucose transporter 2, glucokinase and pancreatic and duodenal homeobox-1) between these two groups. Taken together, these

  5. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    International Nuclear Information System (INIS)

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L.

    2007-01-01

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification

  6. Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring

    International Nuclear Information System (INIS)

    Byun, Hyang-Min; Benachour, Nora; Zalko, Daniel; Frisardi, Maria Chiara; Colicino, Elena; Takser, Larissa; Baccarelli, Andrea A.

    2015-01-01

    Polybrominated diphenyl ethers (PBDEs) are known endocrine disrupting chemicals used commonly as flame retardants in everything from electronics to furniture. Exposure to PBDEs during early development has been linked to neurodevelopmental delays. Despite mounting evidence of neurological harm from PBDE exposure, the molecular mechanisms underlying these effects on brain function remain unknown. We examined the effects of perinatal exposure to BDE-47, the most biologically active and prevalent BDE congener in North America, on epigenetic patterns in the frontal lobe of Wistar rats. Dams were gavaged with BDE-47 (0.002 and 0.2 mg/kg body weight) at gestation days 9 and 16, and postnatal days 1, 8, and 15. Frontal lobes from offspring at postnatal day 41 were collected to measure 5-methylcytosine (5mC) in mitochondrial cytochrome c oxidase genes (Mt-co1, Mt-co2, and Mt-co3), global nuclear 5-hydroxymethylcytosine (5hmC) content, 5mC in repetitive elements L1Rn, and 5mC in nuclear genes (Bdnf, Crhr1, Mc2r, Nr3c1, and Snca) related to behavioral and brain functions in the nuclear genome. We observed a significant decrease in %5mC in Mt-co2 (difference from control = −0.68%, p = 0.01 at the 0.2 mg/kg BDE-47). 5mC in repetitive elements L1Rn decreased at 0.002 mg/kg BDE-47 (difference = −1.23%, p = 0.02). Decreased nuclear 5mC was observed in Bdnf and Nr3c1 in BDE-47 exposed rats. However, we did not observe significant effects of PBDE toxicity on DNA methylation patterns for the majority of genes in the brain

  7. Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring.

    Science.gov (United States)

    Byun, Hyang-Min; Benachour, Nora; Zalko, Daniel; Frisardi, Maria Chiara; Colicino, Elena; Takser, Larissa; Baccarelli, Andrea A

    2015-02-03

    Polybrominated diphenyl ethers (PBDEs) are known endocrine disrupting chemicals used commonly as flame retardants in everything from electronics to furniture. Exposure to PBDEs during early development has been linked to neurodevelopmental delays. Despite mounting evidence of neurological harm from PBDE exposure, the molecular mechanisms underlying these effects on brain function remain unknown. We examined the effects of perinatal exposure to BDE-47, the most biologically active and prevalent BDE congener in North America, on epigenetic patterns in the frontal lobe of Wistar rats. Dams were gavaged with BDE-47 (0.002 and 0.2mg/kg body weight) at gestation days 9 and 16, and postnatal days 1, 8, and 15. Frontal lobes from offspring at postnatal day 41 were collected to measure 5-methylcytosine (5mC) in mitochondrial cytochrome c oxidase genes (Mt-co1, Mt-co2, and Mt-co3), global nuclear 5-hydroxymethylcytosine (5hmC) content, 5mC in repetitive elements L1Rn, and 5mC in nuclear genes (Bdnf, Crhr1, Mc2r, Nr3c1, and Snca) related to behavioral and brain functions in the nuclear genome. We observed a significant decrease in %5mC in Mt-co2 (difference from control=-0.68%, p=0.01 at the 0.2mg/kg BDE-47). 5mC in repetitive elements L1Rn decreased at 0.002 mg/kg BDE-47 (difference=-1.23%, p=0.02). Decreased nuclear 5mC was observed in Bdnf and Nr3c1 in BDE-47 exposed rats. However, we did not observe significant effects of PBDE toxicity on DNA methylation patterns for the majority of genes in the brain. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

    Directory of Open Access Journals (Sweden)

    Megan C. Hallam

    2016-01-01

    Full Text Available The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF had lower body weight and adiposity than animals re-matched to a high protein (HP or control (C diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05. Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones. The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation.

  9. Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats

    Science.gov (United States)

    Hallam, Megan C.; Reimer, Raylene A.

    2016-01-01

    The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation. PMID:26784224

  10. Characterization of biliary conjugates of 4,4'-methylenedianiline in male versus female rats

    International Nuclear Information System (INIS)

    Chen, Kan; Cole, Richard B.; Santa Cruz, Vicente; Blakeney, Ernest W.; Kanz, Mary F.; Dugas, Tammy R.

    2008-01-01

    4,4'-Methylenedianiline (4,4'-diaminodiphenylmethane; DAPM) is an aromatic diamine used in the production of numerous polyurethane foams and epoxy resins. Previous studies in rats revealed that DAPM initially injures biliary epithelial cells of the liver, that the toxicity is greater in female than in male rats, and that the toxic metabolites of DAPM are excreted into bile. Since male and female rats exhibit differences in the expression of both phase I and phase II enzymes, our hypothesis was that female rats either metabolize DAPM to more toxic metabolites or have a decreased capacity to conjugate metabolites to less toxic intermediates. Our objective was thus to isolate, characterize, and quantify DAPM metabolites excreted into bile in both male and female bile duct-cannulated Sprague Dawley rats. The rats were gavaged with [ 14 C]-DAPM, and the collected bile was subjected to reversed-phase HPLC with radioisotope detection. Peaks eluting from HPLC were collected and analyzed using electrospray MS and NMR spectroscopy. HPLC analysis indicated numerous metabolites in both sexes, but male rats excreted greater amounts of glutathione and glucuronide conjugates than females. Electrospray MS and NMR spectra of HPLC fractions revealed that the most prominent metabolite found in bile of both sexes was a glutathione conjugate of an imine metabolite of a 4'-nitroso-DAPM. Seven other metabolites were identified, including acetylated, cysteinyl-glycine, glutamyl-cysteine, glycine, and glucuronide conjugates. While our prior studies demonstrated increased covalent binding of DAPM in the liver and bile of female compared to male rats, in these studies, SDS-PAGE with autoradiography revealed 4-5 radiolabeled protein bands in the bile of rats treated with [ 14 C]-DAPM. In addition, these bands were much more prominent in female than in male rats. These studies thus suggest that a plausible mechanism for the increased sensitivity of female rats to DAPM toxicity may be decreased

  11. A Wide Range of 3243A>G/tRNALeu(UUR) (MELAS) Mutation Loads May Segregate in Offspring through the Female Germline Bottleneck

    Science.gov (United States)

    Pallotti, Francesco; Binelli, Giorgio; Fabbri, Raffaella; Valentino, Maria L.; Vicenti, Rossella; Macciocca, Maria; Cevoli, Sabina; Baruzzi, Agostino; DiMauro, Salvatore; Carelli, Valerio

    2014-01-01

    Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A>G/tRNALeu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated “mother-to-offspring” segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of “segregating units” in the “mother-to-offspring” segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size. PMID:24805791

  12. Effect of Dietary n-3 Polyunsaturated Fatty Acids on Oxidant/Antioxidant Status in Macrosomic Offspring of Diabetic Rats

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    B. Guermouche

    2014-01-01

    Full Text Available The aim of this work was to determine the effect of dietary n-3 PUFA on oxidant/antioxidant status, in vitro very low and low density lipoprotein (VLDL-LDL, and VLDL-LDL-fatty acid composition in macrosomic pups of diabetic mothers. We hypothesized that n-3 PUFA would improve oxidative stress in macrosomia. Diabetes was induced in female Wistar rats fed with the ISIO diet (control or with the EPAX diet (enriched in n-3 PUFAs, by streptozotocin. The macrosomic pups were killed at birth (day 0 and at adulthood (day 90. Lipid parameters and VLDL-LDL-fatty acid composition were investigated. The oxidant/antioxidant status was determined by measuring plasma oxygen radical absorbance capacity (ORAC, hydroperoxides, carbonyl proteins, and VLDL-LDL oxidation. Macrosomic rats of ISIO fed diabetic mothers showed an increase in plasma and VLDL-LDL-triglycerides and VLDL-LDL-cholesterol levels and altered VLDL-LDL-fatty acid composition. Plasma ORAC was low with high hydroperoxide and carbonyl protein levels. The in vitro oxidizability of VLDL-LDL was enhanced in these macrosomic rats. The EPAX diet corrected lipid parameters and improved oxidant/antioxidant status but increased VLDL-LDL susceptibility to oxidation. Macrosomia is associated with lipid abnormalities and oxidative stress. n-3 PUFA exerts favorable effects on lipid metabolism and on the oxidant/antioxidant status of macrosomic rats. However, there are no evident effects on VLDL-LDL oxidation.

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

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    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.

  14. 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.

  15. The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats

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    Rajabzadeh Aliakbar

    2012-05-01

    Full Text Available Abstract Background Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM, which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. Methods Forty timed-pregnant Wistar rats were divided into four groups: A Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy rats that received repeated intraperitoneal (i.p. pentylenetetrazol, PTZ injections on gestational days (GD 14-19; B Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry. Results Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001 and Kind-/Seiz+ (p = 0.001 groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007 and Kind-/Seiz+ (p = 0.007 group’s newborns on both PD1 and 14. Conclusion Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.

  16. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    Directory of Open Access Journals (Sweden)

    Thais de Castro Barbosa

    2016-03-01

    Conclusion: Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.

  17. Maternal vitamin D deficiency during pregnancy results in insulin resistance in rat offspring, which is associated with inflammation and Iκbα methylation.

    Science.gov (United States)

    Zhang, Huaqi; Chu, Xia; Huang, Yifan; Li, Gang; Wang, Yuxia; Li, Ying; Sun, Changhao

    2014-10-01

    We aimed to investigate the impact of maternal vitamin D deficiency during pregnancy on insulin resistance in male offspring and examine its mechanism. Pregnant Sprague-Dawley rats were maintained on a vitamin-D-free diet with ultraviolet-free light during pregnancy (early-VDD group). Insulin resistance in the male offspring was assessed by HOMA-IR, OGTT and euglycaemic clamp. NEFA, oxidative stress and inflammation levels were estimated as risk factors for insulin resistance. DNA methylation was examined by bisulfate sequencing PCR analysis. Luciferase reporter assay was performed to validate the effect of DNA methylation. The offspring in the early-VDD group had significantly higher fasting insulin and HOMA-IR levels, markedly reduced glucose tolerance and significantly lower tissue sensitivity to exogenous insulin at 16 weeks (all p insulin resistance in the offspring, which is associated with persistently increased inflammation. Persistently decreased Iκbα expression, potentially caused by changes in Iκbα methylation, plays an important role in persistent inflammation.

  18. Disturbed nitric oxide and homocysteine production are involved in the increased risk of cardiovascular diseases in the F1 offspring of maternal obesity and malnutrition.

    Science.gov (United States)

    Moussa, Y Y; Tawfik, S H; Haiba, M M; Saad, M I; Hanafi, M Y; Abdelkhalek, T M; Oriquat, G A; Kamel, M A

    2017-06-01

    The present study aimed to evaluate the changes in levels of different independent risk factors for vascular diseases in the rat offspring of maternal obesity and malnutrition as maternal health disturbances are thought to have direct consequences on the offspring health. The effect of postnatal diet on the offspring was also assessed. Three groups of female Wistar rats were used (control, obese and malnourished). After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks postnatal, 20 pups (10 males and 10 females) of each subgroup were sacrificed after overnight fasting, the blood sample was obtained, and the rats were dissected out to obtain heart muscle. The following parameters were assessed; lipid profile, NEFA, homocysteine (Hcy), nitric oxide end product (NOx) and myocardial triglyceride content. Maternal obesity and malnutrition caused significant elevation in the body weight, triglycerides, NEFA, Hcy and NOx in the F1 offspring especially those maintained under HCD. Also, the male offspring showed more prominent changes than female offspring. Maternal malnutrition and obesity may increase the risk of the development of cardiovascular diseases in the offspring, especially the male ones.

  19. Opium can differently alter blood glucose, sodium and potassium in male and female rats.

    Science.gov (United States)

    Karam, Gholamreza Asadi; Rashidinejad, Hamid Reza; Aghaee, Mohammad Mehdi; Ahmadi, Jafar; Rahmani, Mohammad Reza; Mahmoodi, Mehdi; Azin, Hosein; Mirzaee, Mohammad Reza; Khaksari, Mohammad

    2008-04-01

    To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism.

  20. Concomitant Effects of Caffeine and Gamma Irradiation in Female Rats

    International Nuclear Information System (INIS)

    Kafafy, Y. A.

    2004-01-01

    The present study was undertaken to evaluate the protective potential of caffeine as an antioxidant (80 mg/kg b.w.) i.p. injected 1 hr before exposure to a dose of (7 Gy) gamma irradiation in female rats. Alterations in serum lipids, cholesterol, triacylglycerol and fatty acids as well as total proteins, urea and uric acid have been investigated 1, 3 and 7 days post irradiation and /or caffeine treatment. Histological and histochemical changes of the dorsal aorta have been studied 7 days post treatment. Results revealed elevated total lipids, cholesterol, triacylglycerol, beside distortion in fatty acids throughout the whole experimentation period by caffeine pre injection, irradiation application and by dual treatment. Protein and urea were elevated by caffeine or irradiation, while both treatments dropped their levels, whereas uric was decreased by all treatments. Histopathological changes and deposition of sudanophilic material in the dorsal aorta wall were detected by either one or both treatments, which point out a limitation in the protective potential of caffeine

  1. 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...

  2. Supplementation of Mice with Specific Nondigestible Oligosaccharides during Pregnancy or Lactation Leads to Diminished Sensitization and Allergy in the Female Offspring

    NARCIS (Netherlands)

    Hogenkamp, Astrid; Knippels, Leon M J; Garssen, Johan; van Esch, Betty C A M

    2015-01-01

    BACKGROUND: The maternal environment and early life exposure affect immune development in offspring. OBJECTIVE: We investigated whether development of food allergy in offspring is affected by supplementing pregnant or lactating sensitized or nonsensitized mice with a mixture of nondigestible

  3. 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

  4. Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on the development of rat offspring: I. The development of the thyroid hormones-neurotransmitters and adenosinergic system interactions.

    Science.gov (United States)

    Ahmed, O M; Abd El-Tawab, S M; Ahmed, R G

    2010-10-01

    The adequate functioning of the maternal thyroid gland plays an important role to ensure that the offspring develop normally. Thus, maternal hypo- and hyperthyroidism are used from the gestation day 1 to lactation day 21, in general, to recognize the alleged association of offspring abnormalities associated with the different thyroid status. In maternal rats during pregnancy and lactation, hypothyroidism in one group was performed by antithyroid drug, methimazole (MMI) that was added in drinking water at concentration 0.02% and hyperthyroidism in the other group was induced by exogenous thyroxine (T4) (from 50 microg to 200 microg/kg body weight) intragastric administration beside adding 0.002% T4 to the drinking water. The hypothyroid and hyperthyroid states in mothers during pregnancy and lactation periods were confirmed by measuring total thyroxine (TT4) and triiodothyronine (TT3) at gestational day 10 and 10 days post-partum, respectively; the effect was more pronounced at the later period than the first. In offspring of control maternal rats, the free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations were pronouncedly increased as the age progressed from 1 to 3 weeks. In hypothyroid group, a marked decrease in serum FT3, FT4 and GH levels was observed while there was a significant increase in TSH level with age progress as compared with the corresponding control. The reverse pattern to latter state was recorded in hyperthyroid group. The thyroid gland of offspring of hypothyroid group, exhibited some histopathological changes as luminal obliteration of follicles, hyperplasia, fibroblastic proliferation and some degenerative changes throughout the experimental period. The offspring of hyperthyroid rats showed larger and less thyroid follicles with flattened cell lining epithelium, decreased thyroid gland size and some degenerative changes along the experimental period. On the other hand, the biochemical data

  5. Effects of perinatal combined exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and tributyltin (TBT) on rat female reproductive system.

    Science.gov (United States)

    Makita, Yuji

    2008-05-01

    1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is the most prevalent metabolite of DDT used as a pesticide before and tributyltin (TBT) compounds are used primarily as antifouling agents on vessels, ships, and aqua culture facilities, as they exert biocidal actions. Currently, p,p'-DDE and TBT are ubiquitously distributed in the environment and bio-accumulated in marine products, especially fish or shellfish. Thus, oral p,p'-DDE and TBT intake through marine products is demonstrated to be rather high in Japan. Consequently, the fetus and neonate will be exposed to p,p'-DDE and TBT via mother. Therefore, effects of perinatal combined exposure to p,p'-DDE and TBT on the female reproductive system after maturation have been investigated in rat female offspring of dams ingesting 125ppm p,p'-DDE (approximately 10mg/kg) and 25ppm TBT (approximately 2mg/kg) during the perinatal period from gestation to lactation. In the present study, no deleterious reproductive outcomes were recognized in p,p'-DDE and/or TBT-treated dams. In contrast, growth retardation had developed in rat female offspring following perinatal exposure to TBT and sustained even after cessation of exposures. Further, reduced ovarian weights with elevated serum follicle-stimulating hormone (FSH) concentrations were observed in the reproductive system of matured female offspring following perinatal exposure to TBT. At present, biological relevance of these alterations remains unknown, but there is a possibility that these alterations lead to reproductive malfunctions in matured female offspring. Copyright © 2007 Elsevier B.V. All rights reserved.

  6. Aluminium and Acrylamide Disrupt Cerebellum Redox States, Cholinergic Function and Membrane-Bound ATPase in Adult Rats and Their Offspring.

    Science.gov (United States)

    Ghorbel, Imen; Amara, Ibtissem Ben; Ktari, Naourez; Elwej, Awatef; Boudawara, Ons; Boudawara, Tahia; Zeghal, Najiba

    2016-12-01

    Accumulation of aluminium and acrylamide in food is a major source of human exposure. Their adverse effects are well documented, but there is no information about the health problems arising from their combined exposure. The aim of the present study was to examine the possible neurotoxic effects after co-exposure of pregnant and lactating rats to aluminium and acrylamide in order to evaluate redox state, cholinergic function and membrane-bound ATPases in the cerebellum of adult rats and their progeny. Pregnant female rats have received aluminium (50 mg/kg body weight) via drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination from the 14th day of pregnancy until day 14 after delivery. Exposure to these toxicants provoked an increase in malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels and a decrease in SOD, CAT, GPx, Na + K + -ATPase, Mg 2+ -ATPase and AChE activities in the cerebellum of mothers and their suckling pups. A reduction in GSH, NPSH and vitamin C levels was also observed. These changes were confirmed by histological results. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in the cerebellum of mothers and their progeny.

  7. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

    Science.gov (United States)

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-05-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Distribution and speciation of arsenic by transplacental and early life exposure to inorganic arsenic in offspring rats.

    Science.gov (United States)

    Xi, Shuhua; Jin, Yaping; Lv, Xiuqiang; Sun, Guifan

    2010-04-01

    The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO(2) from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood-brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.

  9. Paternity of offspring in multiply-mated, female crickets: the effect of nuptial food gifts and the advantage of mating first

    Science.gov (United States)

    Calos, J. B.; Sakaluk, S. K.

    1998-01-01

    The spermatophore transferred by male decorated crickets (Gryllodes sigillatus) includes a large gelatinous mass, the spermatophylax, that is consumed by the female after mating. This nuptial gift preoccupies the female while sperm are discharged from the remaining portion of the spermatophore, the sperm ampulla, into her reproductive tract. There is considerable variation in the mass of the spermatophylax, and about half of all males produce spermatophylaxes that are too small to ensure complete sperm transfer. We tested two hypotheses concerning the maintenance of this variation: (i) males trade-off investment in spermatophylaxes against copulation frequency; and (ii) males synthesize the largest spermatophylaxes of which they are physiologically capable. Males synthesizing large and small food gifts were permitted multiple mating opportunities with the same females, and allozyme markers were used to establish the paternity of offspring. There was a significant advantage to those males that mated first irrespective of gift size. This advantage probably arose, in part, because the sperm of first males would have had exclusive access to females' eggs during the first 24 hours of oviposition, and underscores the benefits of matings with virgin females. The paternity of 'small-gift' males increased with gift mass, but there was no such increase in 'large-gift' males. This difference probably stems from the relationship between gift mass and sperm transfer: most of the gifts of the large-gift males would have been above the threshold needed to achieve complete inseminations, whereas those of small-gift males would have been below the threshold. Within mating-order positions, there was no significant difference in the paternity of large-gift and small-gift males, a result seemingly consistent with the 'trade-off' hypothesis. However, there was no correlation between spermatophylax mass and male mating frequency, so that the mechanism by which small-gift males offset

  10. Excess androgen during puberty disrupts circadian organization in female rats.

    Science.gov (United States)

    Sellix, Michael T; Murphy, Zachary C; Menaker, Michael

    2013-04-01

    Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.

  11. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure and insulin resistance in offspring rats.

    Science.gov (United States)

    Hao, Xue-Qin; Du, Jing-Xia; Li, Yan; Li, Meng; Zhang, Shou-Yan

    2014-01-01

    Adult metabolic syndrome may in part have origins in fetal or early life. This study was designed to explore the effect of prenatal exposure to lipopolysaccharide and high-fat diet on metabolic syndrome in offspring rats. 32 pregnant rats were randomly divided into four groups, including Control group; LPS group (pregnant rats were injected with LPS 0.4 mg/kg intraperitoneally on the 8(th), 10(th) and 12(th) day of pregnancy); High-fat group (maternal rats had high-fat diet during pregnancy and lactation period, and their pups also had high-fat diet up to the third month of life); LPS + High-fat group (rats were exposed to the identical experimental scheme with LPS group and High-fat group). Blood pressure elevated in LPS group and High-fat group, reduced in LPS+High-fat group, accompanied by the increase of serum leptin level in LPS and High-fat group and increase of serum IL-6, TNF-a in High-fat group; both serum insulin and cholesterol increased in High-fat and LPS+High-fat group, as well as insulin in LPS group. HOMA-IR value increased in LPS, High-fat and LPS+High-fat group, and QUICKI decreased in these groups; H-E staining showed morphologically pathological changes in thoracic aorta and liver tissue in the three groups. Increased serum alanine and aspartate aminotransferase suggest impaired liver function in LPS+High-fat group. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure, insulin resistance and impaired liver function in three-month old offspring rats. The lowered blood pressure might benefit from the predictive adaptive response to prenatal inflammation.

  12. Sex-dependent behavioral changes in rat offspring after in utero administration of a single low dose PBDE 47

    Energy Technology Data Exchange (ETDEWEB)

    Kuriyama, S.N.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

    2004-09-15

    change which could manifest itself in an irreversible fashion at later time points in life. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW of the congener, 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47). These doses are pertinent to human exposure levels because a study by She et al. found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat (10). In this study, peri-pubertal behavior effects were evaluated in rat offspring after in utero administration of low dose PBDE 47.

  13. Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat

    Science.gov (United States)

    Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...

  14. Additive effects of dietary glycotoxins and androgen excess on the kidney of a female rat model

    Directory of Open Access Journals (Sweden)

    Sotiria Palimeri

    2016-06-01

    Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen exposure, exert a more profound negative impact on the kidney of an androgenized female rat model that mimics the metabolic characteristics of polycystic ovary syndrome.

  15. Isoflurane Anesthesia Interferes with the Expression of Cocaine-Induced Sensitization in Female Rats

    OpenAIRE

    Siegal, Nora; Dow-Edwards, Diana

    2009-01-01

    Repeated cocaine administration results in a progressive sensitization of behavior which typically occurs more readily in female rats than in males. Our recent studies of rats undergoing surgical procedures revealed that following anesthesia, females sensitized less than males receiving identical repeated cocaine injections. Since isoflurane acts primarily by increasing the effects of the inhibitory neurotransmitter γ-amino butyric acid (GABA) and reducing the effects of the excitatory amino ...

  16. Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring.

    Science.gov (United States)

    Çetin, Hasan; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Pastacı, Nural; Özkaya, Mehmet Okan

    2014-12-01

    The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Brain and liver glutathione peroxidase activities, as well as liver vitamin A and β-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and β-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the three groups. EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.

  17. A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

    Science.gov (United States)

    Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner

    Directory of Open Access Journals (Sweden)

    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.

  19. Maternal chocolate and sucrose soft drink intake induces hepatic steatosis in rat offspring associated with altered lipid gene expression profile

    DEFF Research Database (Denmark)

    Kjærgaard, Maj; Nilsson, C.; Rosendal, A.

    2014-01-01

    weight gain and adiposity in offspring born to chow-fed dams. Conclusion: Our results suggest that supplementation of chocolate and soft drink during gestation and lactation contributes to early onset of hepatic steatosis associated with changes in hepatic gene expression and lipid handling....... until weaning, giving four dietary groups. Results: At postnatal day 1, offspring from high-fat/high-sucrose-fed dams were heavier and had increased hepatic triglycerides (TG), hepatic glycogen, blood glucose and plasma insulin compared with offspring from chow-fed dams. Hepatic genes involved in lipid...... oxidation, VLDL transport and insulin receptor were down-regulated, whereas FGF21 expression was up-regulated. Independent of postnatal litter size, offspring from high-fat/high-sucrose-fed dams aged 21 days had still increased hepatic TG and up-regulated FGF21 expression, while plasma insulin started...

  20. Males and females contribute unequally to offspring genetic diversity in the polygynandrous mating system of wild boar.

    Directory of Open Access Journals (Sweden)

    Javier Pérez-González

    Full Text Available The maintenance of genetic diversity across generations depends on both the number of reproducing males and females. Variance in reproductive success, multiple paternity and litter size can all affect the relative contributions of male and female parents to genetic variation of progeny. The mating system of the wild boar (Sus scrofa has been described as polygynous, although evidence of multiple paternity in litters has been found. Using 14 microsatellite markers, we evaluated the contribution of males and females to genetic variation in the next generation in independent wild boar populations from the Iberian Peninsula and Hungary. Genetic contributions of males and females were obtained by distinguishing the paternal and maternal genetic component inherited by the progeny. We found that the paternally inherited genetic component of progeny was more diverse than the maternally inherited component. Simulations showed that this finding might be due to a sampling bias. However, after controlling for the bias by fitting both the genetic diversity in the adult population and the number of reproductive individuals in the models, paternally inherited genotypes remained more diverse than those inherited maternally. Our results suggest new insights into how promiscuous mating systems can help maintain genetic variation.

  1. Risk of solid cancer in the offspring of female workers of the Mayak nuclear facility in the Southern Urals, Russian Federation

    International Nuclear Information System (INIS)

    Tsareva, Y.; Sokolnikov, M.; Okatenko, P.; Deltour, I.; Schonfeld, S.J.; Schuez, J.; Vostrotin, V.V.

    2016-01-01

    Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases. (orig.)

  2. Risk of solid cancer in the offspring of female workers of the Mayak nuclear facility in the Southern Urals, Russian Federation

    Energy Technology Data Exchange (ETDEWEB)

    Tsareva, Y.; Sokolnikov, M.; Okatenko, P. [Southern Urals Biophysics Institute (SUBI), Epidemiology Laboratory, Ozyorsk (Russian Federation); Deltour, I.; Schonfeld, S.J.; Schuez, J. [International Agency for Research on Cancer (IARC), Section of Environment and Radiation, Lyon Cedex 08 (France); Vostrotin, V.V. [Southern Urals Biophysics Institute (SUBI), Laboratory of Radiation Safety, Ozyorsk (Russian Federation)

    2016-08-15

    Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases. (orig.)

  3. The role of oxytocin and vasopressin in conditioned mate guarding behavior in the female rat.

    Science.gov (United States)

    Holley, Amanda; Bellevue, Shannon; Vosberg, Daniel; Wenzel, Kerstin; Roorda, Sieger; Pfaus, James G

    2015-05-15

    We have shown previously that female rats given their first copulatory experiences with the same male rat display mate guarding behavior in the presence of that male provided a female competitor is also present. Females given access to the familiar male show more Fos induction within regions of the brain that contain oxytocin (OT) and vasopressin (AVP) cell bodies, notably the supraoptic (SON) and paraventricular nuclei (PVN) relative to females given sexual experience with different males. The present experiments examined whether the Fos induction we previously observed within the SON and PVN occurred within OT and/or AVP neurons, and whether exogenous administration of OT or AVP prior to female rats first sexual experience could potentiate the acquisition of mate guarding behavior. Female rats that display conditioned mate guarding had significantly more double-labeled Fos/OT neurons in both SON and PVN, and significantly more Fos/AVP neurons in the PVN. Peripheral administration of OT or AVP prior to their first sexual experience with the familiar male facilitated different aspects of mate guarding: OT augmented affiliative behaviors and presenting responses whereas AVP augmented interference behavior. These results indicate that female rats' first experiences with sexual reward when paired with the same male induce changes to bonding networks in the brain. Moreover peripheral administration of OT or AVP during their first sexual experience can augment different aspects of mate guarding behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Wistar-Kyoto Female Rats Are More Susceptible to Develop Sugar Binging: A Comparison with Wistar Rats

    Directory of Open Access Journals (Sweden)

    Helena Papacostas-Quintanilla

    2017-05-01

    Full Text Available The hedonic component of the feeding behavior involves the mesolimbic reward system and resembles addictions. Nowadays, the excessive consumption of sucrose is considered addictive. The Wistar-Kyoto (WKY rat strain is prone to develop anxiety and addiction-like behavior; nevertheless, a lack of information regarding their vulnerability to develop sugar binging-like behavior (SBLB and how it affects the reward system persist. Therefore, the first aim of the present study was to compare the different predisposition of two rat strains, Wistar (W and WKY to develop the SBLB in female and male rats. Also, we studied if the SBLB-inducing protocol produces changes in anxiety-like behavior using the plus-maze test (PMT and, analyzed serotonin (5-HT and noradrenaline (NA concentrations in brain areas related to anxiety and ingestive behavior (brain stem, hypothalamus, nucleus accumbens, and amygdala. Finally, we evaluated whether fluoxetine, a drug that has been effective in reducing the binge-eating frequency, body weight, and severity of binge eating disorder, could also block this behavior. Briefly, WKY and W female rats were exposed to 30% sucrose solution (2 h, 3 days/week for 4 weeks, and fed up ad libitum. PMT was performed between the last two test periods. Immediately after the last test where sucrose access was available, rats were decapitated and brain areas extracted for high-performance liquid chromatography analysis. The results showed that both W and WKY female and male rats developed the SBLB. WKY rats consumed more calories and ingested a bigger amount of sucrose solution than their W counterpart. This behavior was reversed by using fluoxetine, rats exposed to the SBLB-inducing protocol presented a rebound effect during the washout period. On female rats, the SBLB-inducing protocol induced changes in NA concentrations on WKY, but not on W rats. No changes were found in 5-HT levels. Finally, animals that developed SBLB showed increased

  5. 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.

  6. Neural mechanisms of female sexual behavior in the rat; comparison with male ejaculatory control.

    NARCIS (Netherlands)

    Veening, J.G.; Coolen, L.M.; Gerrits, P.O.

    2014-01-01

    The sequential organization of sexual behavior of the female rat is described, eventually leading to the lordotic posture, shown during mating. A complex set of signals: olfactory, cutaneous sensory as well as genitosensory, is guiding the female to this specific posture, eventually. Genitosensory

  7. Neural mechanisms of female sexual behavior in the rat; comparison with male ejaculatory control

    NARCIS (Netherlands)

    Veening, J.G.; Coolen, L. M.; Gerrits, P.O.

    The sequential organization of sexual behavior of the female rat is described, eventually leading to the lordotic posture, shown during mating. A complex set of signals: olfactory, cutaneous sensory as well as genitosensory, is guiding the female to this specific posture, eventually. Genitosensory

  8. Pair housing differentially affects motivation to self-administer cocaine in male and female rats.

    Science.gov (United States)

    Westenbroek, Christel; Perry, Adam N; Becker, Jill B

    2013-09-01

    Female rats exhibit greater intake and motivation to self-administer cocaine. In females but not males, isolation by itself is a stressor, which could lead to increased drug intake. Therefore, we hypothesized that social housing would buffer against stress and reduce the motivation to self-administer cocaine primarily in females. Male and female Sprague-Dawley rats were housed individually or in same-sex pairs. The individually housed rats and one of each pair were allowed to self-administer (SA) a low dose of cocaine (0.2 mg/kg/inf) on a fixed ratio (FR1) schedule for one week. Motivation for cocaine SA was measured for an additional 2 weeks on a progressive ratio schedule. Isolated females had greater cocaine-intake on the FR1 schedule and greater motivation to take cocaine than males. Pair-housing in females, but not males, attenuated the motivation to take cocaine. Isolated females, but not males, showed escalation of their motivation to take cocaine, which was attenuated by pair housing of females. Concluding, the motivation to take cocaine escalates in females but not males, and pair-housing of females attenuates this escalation. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2014-05-09

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  10. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    International Nuclear Information System (INIS)

    Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.

    2014-01-01

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse

  11. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Directory of Open Access Journals (Sweden)

    M.F. Souza

    2014-06-01

    Full Text Available Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL, estradiol (0.05 mg/mL, progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  12. Harmful effect of protein difficiency on lipids, glucose, insulin and estradiol levels in female albino rats

    International Nuclear Information System (INIS)

    El-Mahdy, A.A.; El-Sherbiny, E.M.; Bayomi, M.M.

    2005-01-01

    The present study was undertaken to investigate the harmful effect of protein deficient diet on some biochemical activities in serum of female rats. Protein malnutrition is a well known socioeconomic problem in different parts of the world. Many studies were investigated on the biological parameters following protein malnutrition in human and experimental animals. Forty albino female rats were divided into 3 groups. The first group (10 rats) fed 18% protein diet and served as normal control and the other two groups, each contains 15 rats, fed 5% protein for 21 and 45 days, respectively, and served as malnourished groups. The results showed significant decrease in total body weight, serum glucose, insulin and estradiol levels in the third group as well as decrease in the total cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol and triglycerides concentrations that compared to normal control rats

  13. High lipid levels in very low density lipoprotein and intermediate density lipoprotein may cause proteinuria and glomerulosclerosis in aging female analbuminemic rats

    NARCIS (Netherlands)

    Joles, JA; vanGoor, H; vanderHorst, MLC; vanTol, A; Elema, JD; Koomans, HA

    1995-01-01

    BACKGROUND: Male rats are generally more prone to developing renal disease than female rats. However, female Nagase analbuminemic rats (NAR) are profoundly hyperlipidemic and develop proteinuria and glomerulosclerosis after uninephrectomy. Male NAR are less hyperlipidemic and are resistant to

  14. Sprague-Dawley and Fischer Female Rats Differ in Acute Effects of Fluoxetine on Sexual Behavior

    Science.gov (United States)

    Miryala, C.S.J.; Hiegel, C.; Uphouse, L.

    2012-01-01

    Introduction The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT1A receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT1A receptors holds for other rat strains is not known. Aim The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT1A receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Main Outcome Measures Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC50 for inhibition of lordosis behavior was determined. Methods Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Results In both the intact and the hormonally-primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose-dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally-primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT1A receptor agonist. Conclusions Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT1A receptor agonist. Fluoxetine’s inhibition of female rat

  15. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

    OpenAIRE

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2016-01-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxyt...

  16. Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.

    Science.gov (United States)

    Golcu, Doruk; Gebre, Rahiwa Z; Sapolsky, Robert M

    2014-08-01

    The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

    Science.gov (United States)

    Gurecká, Radana; Koborová, Ivana; Janšáková, Katarína; Tábi, Tamás; Szökő, Éva; Somoza, Veronika; Šebeková, Katarína; Celec, Peter

    2015-04-01

    To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life.

  18. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

    Science.gov (United States)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

    2013-07-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach

    International Nuclear Information System (INIS)

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Baghban Khojasteh, Nasrin

    2012-01-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. - Highlights: ► Boron distribution in male and female rats' normal brain was studied in this research. ► Coronal sections of animal tissue samples were irradiated with thermal neutrons. ► Alpha and Lithium tracks were counted using alpha autoradiography. ► Different boron concentration was seen in brain sections of male and female rats. ► The highest boron concentration was seen in 4 h after boron compound injection.

  20. Social transmission of Pavlovian fear: fear-conditioning by-proxy in related female rats.

    Science.gov (United States)

    Jones, Carolyn E; Riha, Penny D; Gore, Andrea C; Monfils, Marie-H

    2014-05-01

    Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing). Individuals can also acquire fear from a social context, such as through observing the fear expression of a conspecific. In the current study, we examined the influence of kinship/familiarity on social transmission of fear in female rats. Rats were housed in triads with either sisters or non-related females. One rat from each cage was fear conditioned to a tone CS+ shock US. On day two, the conditioned rat was returned to the chamber accompanied by one of her cage mates. Both rats were allowed to behave freely, while the tone was played in the absence of the foot-shock. The previously untrained rat is referred to as the fear-conditioned by-proxy (FCbP) animal, as she would freeze based on observations of her cage-mate's response rather than due to direct personal experience with the foot-shock. The third rat served as a cage-mate control. The third day, long-term memory tests to the CS were performed. Consistent with our previous application of this paradigm in male rats (Bruchey et al. in Behav Brain Res 214(1):80-84, 2010), our results revealed that social interactions between the fear conditioned and FCbP rats on day two contribute to freezing displayed by the FCbP rats on day three. In this experiment, prosocial behavior occurring at the termination of the cue on day two was significantly greater between sisters than their non-sister counterparts, and this behavior resulted in increased freezing on day three. Our results suggest that familiarity and/or kinship influences the social transmission of fear in female rats.

  1. Effects of early gestational all-trans retinoic acid treatment on motor skills: a longitudinal study in the offspring of Sprague-Dawley rats.

    Science.gov (United States)

    Coluccia, Addolorata; Borracci, Pietro; Belfiore, Domenico; Renna, Giuseppe; Giustino, Arcangela; Carratù, Maria Rosaria

    2008-11-01

    The purpose of the present study was to investigate the behavioral outcomes of all-trans retinoic acid (RA) treatment in the period spanning gestational day (GD) 8-10. A sublethal dose (2.5mg/kg b.w.) compatible with high neonatal survival, sufficient to supply male offspring for later behavioral testing, was used. Indeed, the mortality rate at birth was 7.8%. Reproduction parameters (body weight gain of dams during gestation, number of dams giving birth, pregnancy length, litter size at birth), offspring body weight gain and the development of their somatic characteristics (ear unfolding, auditory conduit opening, eyes opening, hair growth) were not altered by RA. Instead, the onset of righting reflex and negative geotaxis were delayed by 2 days, suggesting vestibular involvement and abnormal functioning of the cerebellum. Then, the performance of RA-treated rats on open field and rotarod/accelerod tasks was assessed from postnatal day (PND) 21 to 90. Similar to the previously investigated GD 11-13 RA treatment, the GD 8-10 RA treatment impaired the open field activity and rotarod/accelerod performance in young adult rats, thus suggesting a task-specific rather than a stage-specific effect of low-dose retinoids during brain development. The delayed appearance of these outcomes underlines the relevance of longitudinal studies to sort out specific RA-targeted neurochemical-behavioral pathways that could be labelled as having no phenotype based on standard examination at birth.

  2. A comparative study of the anorectic and behavioral effects of fenproporex on male and female rats.

    Science.gov (United States)

    Mattei, R; Carlini, E A

    1996-08-01

    The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, ip) and methamphetamine (Met, 2.5 mg/kg, ip), a prototypical example of an amphetamine-like drug, were studied in male and female Wistar rats (5 and 3 months of age, respectively, at the beginning of the experiments) after acute (immediately after a single dose) or chronic treatment (after 60 days of administration). For the evaluation of the experimental parameters six groups of eight rats each were utilized for food intake and stereotyped behavior and six groups of nine rats each for body weight and motor activity. Similar anorectic effects (decreased food intake in grams: saline (Sal): 12.8 +/- 2.5, Met: 4.7 +/- 4.0, and Fenp: 4.4 +/- 20; decreased weight gain: Sal: 38 +/- 10, Met: 25 +/- 1.0, and Fenp: 27 +/- 3.0) were induced by both drugs in male rats. Female rats, however, required larger doses (20 mg/kg Fenp and 5.0 mg/kg Met) for a complete blockade of food intake. The behavioral tests were carried out 30, 60, 120, 180 and 300 min after drug administration and on day 1 and day 60 immediately after the treatment, for stereotypy and motor activity, respectively (male rats: Met: 3.8 +/- 0.3, Fenp: 6.0 +/- 0.9, and female rats: Met: 15.4 +/- 1.9, Fenp: 9.7 +/- 1.3). Though stereotyped behavior such as sniffing, continuous licking, and false bites was observed in all animals, this was more evident and prolonged in female rats. Both drugs also increased motor activity (male rats, acute treatment: Met: 608 +/- 419, Fenp: 677 +/- 354; chronic treatment: Met: 701 +/- 423, Fenp: 908 +/- 479; female rats, acute treatment: Met: 817 +/- 350, Fenp: 1177 +/- 282; chronic treatment: Met: 623 +/- 274, Fenp: 1511 +/- 573) with female rats once again showing greater sensitivity both after acute and chronic treatment. Our data indicate that fenproporex, like methamphetamine, has a stimulating effect on the central nervous system, indicating an action on the dopaminergic systems. These data further suggest

  3. 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

  4. Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats.

    Science.gov (United States)

    Lalanza, Jaume F; Sanchez-Roige, Sandra; Cigarroa, Igor; Gagliano, Humberto; Fuentes, Silvia; Armario, Antonio; Capdevila, Lluís; Escorihuela, Rosa M

    2015-11-05

    Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non-handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders.

  5. Perinatal fluoxetine effects on social play, the HPA system, and hippocampal plasticity in pre-adolescent male and female rats: Interactions with pre-gestational maternal stress.

    Science.gov (United States)

    Gemmel, Mary; Hazlett, Mariah; Bögi, Eszter; De Lacalle, Sonsoles; Hill, Lesley A; Kokras, Nikolaos; Hammond, Geoffrey L; Dalla, Christina; Charlier, Thierry D; Pawluski, Jodi L

    2017-10-01

    Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the

  6. 20neon ion- and x-ray-induced mammary carcinogenesis in female rats

    International Nuclear Information System (INIS)

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to 20 Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for 20 Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that 20 Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

  7. Effects of Di-(2-ethylhexyl Phthalate on the Hypothalamus–Uterus in Pubertal Female Rats

    Directory of Open Access Journals (Sweden)

    Te Liu

    2016-11-01

    Full Text Available The pollution of endocrine disruptors and its impact on human reproductive system have attracted much attention. Di-(2-ethylhexyl phthalate (DEHP, an environmental endocrine disruptor, is widely used in food packages, containers, medical supplies and children’s toys. It can cause diseases such as infertility, sexual precocity and uterine bleeding and thus arouse concerns from the society and scholars. The effect of DEHP on pubertal female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on the hypothalamus–uterus in pubertal female rats, reveal the reproductive toxicity of DEHP on pubertal female rats and its mechanism, and provide scientific evidence for the evaluation of toxicity and toxic mechanism of DEHP on reproductive system. Forty-eight pubertal female rats were randomly divided into four groups and respectively administered via oral gavage 0, 250, 500, or 1000 mg/kg/d DEHP in 0.1 mL corn oil/20 g body weight for up to four weeks. Compared with control rats, the DEHP-treated rats showed: (1 higher gonadotropin-releasing hormone (GnRH level in the hypothalamus; (2 higher protein levels of GnRH in the hypothalamus; and (3 higher mRNA and protein levels of GnRH receptor (GnRHR in the uterus. Our data reveal that DEHP exposure may lead to a disruption in pubertal female rats and an imbalance of hypothalamus–uterus. Meanwhile, DEHP may, through the GnRH in the hypothalamus and its receptor on the uterus, lead to diseases of the uterus. DEHP may impose a negative influence on the development and functioning of the reproductive system in pubertal female rats.

  8. Effects of Di-(2-ethylhexyl) Phthalate on the Hypothalamus–Uterus in Pubertal Female Rats

    Science.gov (United States)

    Liu, Te; Jia, Yiyang; Zhou, Liting; Wang, Qi; Sun, Di; Xu, Jin; Wu, Juan; Chen, Huaiji; Xu, Feng; Ye, Lin

    2016-01-01

    The pollution of endocrine disruptors and its impact on human reproductive system have attracted much attention. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely used in food packages, containers, medical supplies and children’s toys. It can cause diseases such as infertility, sexual precocity and uterine bleeding and thus arouse concerns from the society and scholars. The effect of DEHP on pubertal female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on the hypothalamus–uterus in pubertal female rats, reveal the reproductive toxicity of DEHP on pubertal female rats and its mechanism, and provide scientific evidence for the evaluation of toxicity and toxic mechanism of DEHP on reproductive system. Forty-eight pubertal female rats were randomly divided into four groups and respectively administered via oral gavage 0, 250, 500, or 1000 mg/kg/d DEHP in 0.1 mL corn oil/20 g body weight for up to four weeks. Compared with control rats, the DEHP-treated rats showed: (1) higher gonadotropin-releasing hormone (GnRH) level in the hypothalamus; (2) higher protein levels of GnRH in the hypothalamus; and (3) higher mRNA and protein levels of GnRH receptor (GnRHR) in the uterus. Our data reveal that DEHP exposure may lead to a disruption in pubertal female rats and an imbalance of hypothalamus–uterus. Meanwhile, DEHP may, through the GnRH in the hypothalamus and its receptor on the uterus, lead to diseases of the uterus. DEHP may impose a negative influence on the development and functioning of the reproductive system in pubertal female rats. PMID:27845755

  9. 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.

  10. 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...

  11. 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.

  12. Pharmacological manipulation of serotonin receptors during brain embryogenesis favours stress resiliency in female rats

    Directory of Open Access Journals (Sweden)

    Gianluca Lavanco

    2018-02-01

    Full Text Available Manipulations of the serotonin transmission during early development induce long-lasting changes in the serotonergic circuitry throughout the brain. However, little is known on the developmental consequences in the female progeny. Therefore, this study aimed at exploring the behavioural effects of pre- and postnatal stimulation of the serotonergic system by 5-methoxytryptamine in adolescent female rats on behavioural reactivity and anxiety- like phenotype. Our results show that perinatal 5- methoxythyptamine decreased total distance travelled and rearing frequency in the novel enviroment, and increased the preference for the centre of the arena in the open field test. Moreover, perinatal 5-methoxytryptamine increased the percentages of entries and time spent on the open arms of the elevated plus maze, with respect to perinatally vehicle-exposed rats. Thus, perinatal stimulation of serotonin receptors does not impair the functional response to the emotional challenges in female rats, favouring the occurrence of a stress-resilient phenotype.

  13. [New data on olfactory control of estral receptivity of female rats].

    Science.gov (United States)

    Satli, M A; Aron, C

    1976-03-01

    Olfactory bulb deprivation increased sexual receptivity in 4-day cyclic female rats on the late afternoon of prooestrus (6-7, p.m.). The proportion of receptive females was higher in bulbectomized (B) than in sham operated (SH) animals. On the contrary the same proportion of B and SH females mated in the evening of prooestrus (10. 30-11. 30 p.m.). An increased lordosis quotient was observed in the B females at either of these two stages of the cycle.

  14. Possible Outcome of Fenugreek Seeds Powder Administration on the Fertility of Female and Male Albino Rat

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, M F; El-Tawill, G.A., E-mail: gkyrillos@hotmail.co [Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2010-07-01

    Fenugreek (Trigonella foenum-graecum) is an annual plant from the family of Papilionaceae-Leguminosae that has been credited with many medicinal properties. The current study aims to evaluate the possible fertility activity of fenugreek seeds powder on female and male albino rats. To achieve the theme, fenugreek seeds powder (200 mg/rat) were daily administered orally to both female and male Wistar rats for 15 and 30 consecutive days, after which the rats were sacrificed for both biochemical and histopathological observations. Fenugreek treatment significantly decreased the serum cholesterol levels in both female and male rats with a marked increase in the ovary and testis cholesterol levels following 30 days of consecutive administration. The circulating serum female hormones showed an initial elevation at the end of 15 days of fenugreek intake followed by a significant drop in the group of rats that continued to receive the daily fenugreek dose for 30 days. These observations were supported by the notable decline in the ovarian weights further validated by their ovarian histological sections revealing remarkable dissolution of some follicles and prominent abundance of inflammatory cells. In the 30 days interval treated males, the serum testosterone hormone concentrations significantly declined and the testis weights were reduced with evident damage to the seminiferous tubules and interstitial tissues as shown by the histopathological picture of testis tissue sections. Accordingly, it can be deduced that fenugreek seeds powder exert a significant antifertility adverse effect on the female and male rats when supplemented at a considerable dose for an extended time interval

  15. Effects of Environmental Conditions on Activity, Feeding, and Body Weight in Male and Female Adolescent Rats

    Science.gov (United States)

    2006-03-31

    marshmallows , etc.) gained more weight than did the rats that were provided standard chow. The animals with access to the activity wheel (activity...salami, cheese, bananas, marshmallows , milk chocolate, and peanut butter (Sclafani & Springer, 1976). In fact, adult female rats given constant...them foods that are high in fat and sugar through foods usually used for human consumption such as cream filled cookies, marshmallows , milk chocolate

  16. Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats.

    Science.gov (United States)

    Martino-Andrade, Anderson J; Morais, Rosana N; Spercoski, Katherinne M; Rossi, Stefani C; Vechi, Marina F; Golin, Munisa; Lombardi, Natália F; Greca, Cláudio S; Dalsenter, Paulo R

    2010-01-08

    Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  17. Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

    Science.gov (United States)

    Pallarés, María Eugenia; Adrover, Ezequiela; Baier, Carlos Javier; Bourguignon, Nadia S; Monteleone, Melisa C; Brocco, Marcela A; González-Calvar, Silvia I; Antonelli, Marta C

    2013-07-01

    Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.

  18. Ventilatory drive is enhanced in male and female rats following chronic intermittent hypoxia.

    Science.gov (United States)

    Edge, D; Skelly, J R; Bradford, A; O'Halloran, K D

    2009-01-01

    Obstructive sleep apnoea is characterized by chronic intermittent hypoxia (CIH) due to recurrent apnoea. We have developed a rat model of CIH, which shows evidence of impaired respiratory muscle function. In this study, we wished to characterize the ventilatory effects of CIH in conscious male and female animals. Adult male (n=14) and female (n=8) Wistar rats were used. Animals were placed in chambers daily for 8 h with free access to food and water. The gas supply to one half of the chambers alternated between air and nitrogen every 90 s, for 8 h per day, reducing ambient oxygen concentration in the chambers to 5% at the nadir (intermittent hypoxia; n=7 male, n=4 female). Air supplying the other chambers was switched every 90 s to air from a separate source, at the same flow rates, and animals in these chambers served as controls (n=7 male, n=4 female). Ventilatory measurements were made in conscious animals (typically sleeping) after 10 days using whole-body plethysmography. Normoxic ventilation was increased in both male and female CIH-treated rats compared to controls but this did not achieve statistical significance. However, ventilatory drive was increased in CIH-treated rats of both sexes as evidenced by significant increases in mean and peak inspiratory flow. Ventilatory responses to acute hypoxia (F(I)O(2) = 0.10; 6 min) and hyperoxic hypercapnia (F(I)CO(2) = 0.05; 6 min) were unaffected by CIH treatment in male and female rats (P>0.05, ANOVA). We conclude that CIH increases respiratory drive in adult rats. We speculate that this represents a form of neural plasticity that may compensate for respiratory muscle impairment that occurs in this animal model.

  19. Impact of three endocrine disruptors, Bisphenol A, Genistein and Vinclozolin on female rat enamel.

    Science.gov (United States)

    Jedeon, K; Berdal, A; Babajko, A

    2016-06-28

    Concerns about the potential adverse effectsof endocrine disruptors (EDs) have been increasingover the last three decades. BisphenolA (BPA), genistein (G) and vinclozolin (V) arethree widely used EDs sharing similar effects.Since populations are exposed to many diverseEDs simultaneously, we demonstratedrecently their impact alone or combined onmale rat tooth enamel. The purpose of thisstudy was therefore to assess their effects onfemale rat tooth enamel in order to understandwhy they are differentially sensitive. Ratswere exposed daily in utero and after birth tolow doses of EDs during the critical fetal andsuckling periods when amelogenesis takesplace. Enamel of rats exposed to EDs presentedopaque areas of hypomineralization. Theproportion of affected rats was the highestin the groups of rats treated with BPA aloneand higher in males than in females (in all thegroups). Comparison of enamel key gene expressionlevels showed modulations of Klk4and Enamelin in males but no significant variationsin females. These findings show thatfemale rats are less affected than males bythe three EDs chosen in this study and suggestthat enamel hypomineralization may differbetween males and females.

  20. Neurogenesis in the olfactory bulb induced by paced mating in the female rat is opioid dependent.

    Directory of Open Access Journals (Sweden)

    Marianela Santoyo-Zedillo

    Full Text Available The possibility to control the rate of sexual stimulation that the female rat receives during a mating encounter (pacing increases the number of newborn neurons that reach the granular layer of the accessory olfactory bulb (AOB. If females mate repeatedly, the increase in the number of neurons is observed in other regions of the AOB and in the main olfactory bulb (MOB. It has also been shown that paced mating induces a reward state mediated by opioids. There is also evidence that opioids modulate neurogenesis. In the present study, we evaluated whether the opioid receptor antagonist naloxone (NX could reduce the increase in neurogenesis in the AOB induced by paced mating. Ovariectomized female rats were randomly divided in 5 different groups: 1 Control (not mated treated with saline, 2 control (not mated treated with naloxone, 3 females that mated without controlling the sexual interaction (no-pacing, 4 females injected with saline before pacing the sexual interaction and 5 females injected with NX before a paced mating session. We found, as previously described, that paced mating induced a higher number of new cells in the granular layer of the AOB. The administration of NX before paced mating, blocked the increase in the number of newborn cells and prevented these cells from differentiating into neurons. These data suggest that opioid peptides play a fundamental role in the neurogenesis induced by paced mating in female rats.

  1. Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats

    Directory of Open Access Journals (Sweden)

    Rafaela G. Feresin

    2014-01-01

    Full Text Available Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD, recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4 vertebrae from leptin receptor-deficient female (Leprfa/fa Zucker rats and their heterozygous lean controls (Leprfa/+ that were either sham-operated or ovariectomized (Ovx. BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P<0.001 decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P<0.001 were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th (P<0.005 than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats.

  2. Effects of irradiation and adrenal cortex disfunction on ovarial-hormonal status of mature female rats

    International Nuclear Information System (INIS)

    Konoplya, E.F.; Banetskaya, N.V.; Sechko, L.K.; Pavlenko, V.S.; Popov, E.G.

    2003-01-01

    It was shown that development of glucocorticoid disfunction in mature rats (made by series of 10 mg/kg body wt subcutaneous corticosterone injections, during I month) essentially increased radiosensitivity of female reproductive organs. Additionally in the experimental conditions after external g-irradiation (1.0 Gy) development of atrophic processes in follicular apparatus of ovary caused severe ovarial disorders (polycystosis, fibrosis). Simultaneously degree of hormonal misregulations and upsets for systems of hormone reception in female sex tissues is aggravating. (authors)

  3. Effects of female gonadal hormones and LPS on depressive-like behavior in rats

    Directory of Open Access Journals (Sweden)

    Mitić Miloš

    2015-01-01

    Full Text Available Considerable evidence shows an association of depression with the immune system and emphasizes the importance of gender in the etiology of the disease and the response to inflammatory stimuli. We examined the influence of immune-challenged systems on depressive-like behavior in female rats in the context of gonadal hormones. We used a neuroinflammatory model of depression elicited by lipopolysaccharide (LPS administration on naive and ovariectomized (OVX female rats, and examined the effects of estradiol (E2 and/or progesterone (P4 replacement therapy on animal behavior, as assessed by the forced swimming test (FST. We found that LPS and OVX increase immobility in the FST, while LPS also decreased body weight in naive female rats. Further, even though P4 application alone showed beneficial effects on the behavioral profile (it reduced immobility and increased climbing, supplementation of both hormones (E2 and P4 together to OVX rats failed to do so. When OVX rats were exposed to LPS-induced immune challenge, neither hormone individually nor their combination had any effect on immobility, however, their joint supplementation increased climbing behavior. In conclusion, our study confirmed that both LPS and OVX induced depressive-like behavior in female rats. Furthermore, our results potentiate P4 supplementation in relieving the depressive-like symptomatology in OVX rats, most likely through fine-tuning of different neurotransmitter systems. In the context of an activated immune system, the application of E2 and/or P4 does not provide any advantageous effects on depressive-like behavior.

  4. Role of Oestrogen α Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment.

    Science.gov (United States)

    Snoeren, E M S; Antonio-Cabrera, E; Spiteri, T; Musatov, S; Ogawa, S; Pfaff, D W; Ågmo, A

    2015-11-01

    The present study investigated the role of oestrogen receptor (ER)α in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ERα to reduce the number of ERα in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8 days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. © 2015 British Society for Neuroendocrinology.

  5. A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

    Science.gov (United States)

    Cuthbert, Candace E; Foster, Jerome E; Ramdath, D Dan

    2017-10-01

    A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (Pinsulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

  6. Effects of ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) derivatives on penetration of /sup 169/Yb and /sup 144/Ce into the rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Baltrukiewicz, Z; Burakowski, T; Derecki, J

    1976-01-01

    Penetration of radioactive ytterbium-169 and cerium-144 into fetuses was determined at the end of pregnancy and penetration into suckling rats was studied during feeding with the milk of exposed mothers when EDTA or DTPA derivatives were being administered. Injection of ytterbium-169 as a complex with EDTA or DTPA or injection of Na/sub 2/Ca EDTA or Na/sub 3/Ca DTPA 1h after administration of cerium-144 to mothers reduced penetration of both radionuclides into offsprings in relation to the animals receiving no complex compounds. It was observed that the action of DTPA was stronger than that of EDTA. Passage of ytterbium with milk and across the placenta was greater than the passage of cerium.

  7. Effects of ethylenediaminetetraacetic acid (EDTA)and diethylenetriaminepentaacetic acid (DTPA) derivatives on penetration of ytterbium-169 and cerium-144 into the rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Baltrukiewicz, Z; Burakowski, T; Derecki, J [Wojskowy Inst. Higieny i Epidemiologii, Warsaw (Poland)

    1976-01-01

    Penetration of radioactive ytterbum-169 and cerium-144 into fetuses was determined at the end of pregnancy and penetration into the organism of suckling rats was studied during feeding with the milk of exposed mothers when EDTA or DTPA derivatives were being administered. Injection of ytterbum-169 as a complex with EDTA or DTPA or injection of Na/sub 2/Ca EDTA or Na/sub 3/Ca DTPA 1h after administration of cerium-144 to mothers reduced penetration of both radionuclides into offsprings in relation to the animals receiving no complex compounds. It was observed that the action of DTPA was stronger than that of EDTA. Passage of ytterbium with milk and across the placenta was greater than the passage of cerium.

  8. Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

    Science.gov (United States)

    Andersen, Monica L; Ribeiro, Daniel A; Alvarenga, Tathiana A; Silva, Andressa; Araujo, Paula; Zager, Adriano; Tenorio, Neuli M; Tufik, Sergio

    2010-02-01

    The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones. Copyright 2009 Elsevier Inc. All rights reserved.

  9. Cyclic estrogenic fluctuation influences synaptic transmission of the medial vestibular nuclei in female rats.

    Science.gov (United States)

    Pettorossi, Vito E; Frondaroli, Adele; Grassi, Silvarosa

    2011-04-01

    The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17β-estradiol (cE(2)). The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE(2) influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2) (nE(2)) from testosterone (T). We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T enzymes were used. Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE.

  10. Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats

    NARCIS (Netherlands)

    Zeinoaldini, S.; Swarts, J.J.M.; Heijning, van de B.J.M.

    2006-01-01

    Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset

  11. Administration of the Antioxidant N-Acetyl-Cysteine in Pregnant Mice Has Long-Term Positive Effects on Metabolic and Behavioral Endpoints of Male and Female Offspring Prenatally Exposed to a High-Fat Diet.

    Science.gov (United States)

    Berry, Alessandra; Bellisario, Veronica; Panetta, Pamela; Raggi, Carla; Magnifico, Maria C; Arese, Marzia; Cirulli, Francesca

    2018-01-01

    A growing body of evidence suggests the consumption of high-fat diet (HFD) during pregnancy to model maternal obesity and the associated increase in oxidative stress (OS), might act as powerful prenatal stressors, leading to adult stress-related metabolic or behavioral disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy) on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13 weeks (from 5-weeks of age until delivery) and were exposed to the N-acetyl-cysteine (NAC) antioxidant from 10-weeks of age until right before delivery. Body weight of the offspring was assessed following birth, up to weaning and at adulthood. The metabolic, neuroendocrine and emotional profile of the adult offspring was tested at 3-months of age. Prenatal HFD increased mother's body weight and offspring's weight at the time of weaning, when administered in conjunction with NAC. In females, NAC administration reduced high levels of leptin resulting from prenatal HFD. Prenatal NAC administration also resulted in greater glucose tolerance and insulin sensitivity while increasing adiponectin levels, as well as increasing exploratory behavior, an effect accompanied by reduced plasma corticosterone levels in response to restraint stress. Analysis of glutathione levels in the hypothalamus and in brown adipose tissue indicates that, while HFD administration to pregnant dams led to reduced levels of glutathione in the offspring, as in the male hypothalamus, NAC was able to revert this effect and to increase glutathione levels both in the periphery (Brown Adipose Tissue, both males and females) and in the central nervous system (males). Overall, results from this study indicate that the body redox milieu should be tightly regulated during fetal life and that buffering OS during pregnancy can have important long

  12. PROTEINURIA, LIPOPROTEINS AND RENAL APOLIPOPROTEIN DEPOSITS IN UNINEPHRECTOMIZED FEMALE ANALBUMINEMIC RATS

    NARCIS (Netherlands)

    JOLES, JA; VANGOOR, H; BRAAM, B; WILLEKESKOOLSCHIJN, N; JANSEN, EHJM; VANTOL, A; KOOMANS, HA

    To elucidate the pathogenetic role of hyperlipidemia per se in the development of glomerulosclerosis, severely hyperlipidemic female analbuminemic rats (NAR) and mildly hyperlipidemic male NAR were studied for a period of 37 weeks after uninephrectomy (UNX). Plasma cholesterol increased from 6.3 +/-

  13. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

    DEFF Research Database (Denmark)

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie

    2015-01-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures...

  14. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats.

    NARCIS (Netherlands)

    Wijk, van N.; Rijntjes, E.; Heijning, van de B.J.

    2008-01-01

    Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the

  15. Increasing intake of soybean protein or casein, but not cod meal, reduces nephrocalcinosis in female rats.

    NARCIS (Netherlands)

    Zhang, X.; Beynen, A.C.

    1992-01-01

    Female weanling rats were fed diets with soybean protein, casein or cod meal at 171, 342 or 513 mmol nitrogen/100 g for 3 wk. The diets were isonitrogenous and balanced for fat, cholesterol, calcium, magnesium and phosphorus. Cod meal feeding at 171 and 342 mmol nitrogen/100 g diet produced lower

  16. Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female rats.

    Science.gov (United States)

    Peysepar, Elham; Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

    2016-01-01

    Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. Sixty Wistar male and female rats were used in eight experimental groups. Both genders received GABA (50 μg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.) was added from day 8 to the end of the study, and they were compared with the control groups. At the end of the study, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage was also determined via staining. CP significantly increased the serum levels of Cr and BUN, kidney weight, and kidney tissue damage score in both genders (PGABA did not attenuate these markers in males; even these biomarkers were intensified in females. Serum level of Mg, and testis and uterus weights did not alter in the groups. However, the groups were significantly different in terms of nitrite and MDA levels. It seems that GABA did not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal damage in female rats.

  17. Leptin and glucocorticoid signaling pathways in the hypothalamus of female and male fructose-fed rats

    Directory of Open Access Journals (Sweden)

    Vojnović-Milutinović Danijela

    2014-01-01

    Full Text Available Alterations in leptin and glucocorticoid signaling pathways in the hypothalamus of male and female rats subjected to a fructose-enriched diet were studied. The level of expression of the key components of the leptin signaling pathway (neuropeptide Y /NPY/ and suppressor of cytokine signaling 3 /SOCS3/, and the glucocorticoid signaling pathway (glucocorticoid receptor /GR/, 11β-hydroxysteroid dehydrogenase type 1 /11βHSD1/ and hexose-6-phosphate dehydrogenase /H6PDH/ did not differ between fructose-fed rats and control animals of both genders. However, in females, a fructose-enriched diet provoked increases in the adiposity index, plasma leptin and triglyceride concentrations, and displayed a tendency to decrease the leptin receptor (ObRb protein and mRNA levels. In male rats, the fructose diet caused elevations in plasma non-esterified fatty acids and triglycerides, as well as in both plasma and hypothalamic leptin concentrations. Our results suggest that a fructose-enriched diet can induce hyperleptinemia in both female and male rats, but with a more pronounced effect on hypothalamic leptin sensitivity in females, probably contributing to the observed development of visceral adiposity. [Projekat Ministarstva nauke Republike Srbije, br. III41009

  18. 17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

    Science.gov (United States)

    Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

    2013-01-01

    Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…