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Sample records for male offspring mice

  1. Therapeutic Effect of Taurine on Gamma Radiation Induced Genetic Injuries in Germ Cells of Male Mice and Their Male Offspring

    El-Dawy, H.A.; Tawfik, S.S.; El-Khafif, M.A.; Ragab, M.H.

    2005-01-01

    The efficiency of taurine therapy for treatment of male mice exposed to a dose of (3 Gy) whole body gamma irradiation and their male offspring was studied after administration taurine 1% in drinking water post irradiation. Administration of taurine therapy resulted in a significant decrease in the effect of irradiation on chromosomal aberrations in irradiated animals and their male offspring. The efficiency of taurine as radio therapeutic agent is greatly dependent on its chemical properties as strong oxidants scavenger and biological activities as osmoregulator and membrane stabilizer. The probable mechanism of taurine therapy was discussed

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

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

    2017-04-15

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

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

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

    2000-01-01

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

  4. High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

    Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

    2013-01-01

    The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

  5. Influence of electromagnetic pulse on the offspring sex ratio of male BALB/c mice.

    Li, Jin-Hui; Jiang, Da-Peng; Wang, Ya-Feng; Yan, Jia-Jia; Guo, Qi-Yan; Miao, Xia; Lang, Hai-Yang; Xu, Sheng-Long; Liu, Jun-Ye; Guo, Guo-Zhen

    2017-09-01

    Public concern is growing about the exposure to electromagnetic fields (EMF) and its effect on male reproductive health. Detrimental effect of EMF exposure on sex hormones, reproductive performance and sex-ratio was reported. The present study was designed to clarify whether paternal exposure to electromagnetic pulse (EMP) affects offspring sex ratio in mice. 50 male BALB/c mice aged 5-6 weeks were exposed to EMP daily for 2 weeks before mated with non-exposed females at 0d, 7d, 14d, 21d and 28d after exposure. Sex hormones including total testosterone, LH, FSH, and GnRH were detected using radioimmunoassay. The sex ratio was examined by PCR and agarose gel electrophoresis. The results of D0, D21 and D28 showed significant increases compared with sham-exposed groups. The serum testosterone increased significantly in D0, D14, D21, and D28 compared with sham-exposed groups (p<0.05). Overall, this study suggested that EMP exposure may lead to the disturbance of reproductive hormone levels and affect the offspring sex ratio. Copyright © 2017. Published by Elsevier B.V.

  6. Carbon black nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice

    El-Sayed, Yasser S.; Shimizu, Ryuhei; Onoda, Atsuto; Takeda, Ken; Umezawa, Masakazu

    2015-01-01

    Increasing exposure to nanoparticles (NPs) has raised concerns regarding their health and safety profiles in humans and animals, especially in developing organisms, which may display increased sensitivity to NP toxicity. The present study examined the effects of gestational exposure to carbon black NP (CB-NP) on the development of the offspring immune system. Pregnant mice were exposed to CB-NP (95 μg/kg body weight) by intranasal instillation on gestational days 9 and 15. The thymus and spleen were collected from their offspring mice on postnatal day (PND) 1, 3 and 5. Thymocyte and splenocyte phenotypes were examined by determining the expression of cell-surface molecules using flow cytometry. Gene expression in the thymus and spleen was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Prenatal exposure to CB-NP increased total thymocytes and their immunophenotypes (CD4 − CD8 − and CD4 + CD8 + cells). It also induced an increase in total lymphocytes, and CD4 − CD8 − , particularly CD3 − B220 − cells, at PND 5 in the spleen of newborn male offspring, reflecting the stimulation of immature splenocytes. Furthermore, mRNA expression of genes related to the induction of peripheral tolerance (i.e. thymic Traf6) was upregulated. These data suggest that respiratory exposure to CB-NP during middle and late gestation may have allergic or inflammatory effects in male offspring, and may provide initial information on the potential developmental immunotoxicity of nanoparticles

  7. Adsorption of Bisphenol A to a Carbon Nanotube Reduced Its Endocrine Disrupting Effect in Mice Male Offspring

    Wenwei Wang

    2014-09-01

    Full Text Available Soluble carbon nanotubes (CNTs have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA, due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties of both BPA and CNTs, and induce different toxicity to human and living systems from that of BPA and CNTs alone. Herein, we report that oral exposure of BPA/MWCNT–COOH (carboxylated multi-walled carbon nantubes adduct to mice during gestation and lactation period decreased the male offspring reproductive toxicity compared with those induced by BPA alone. The adduct decreased malondialdehyde (MDA level in testis and follicle-stimulating hormone (FSH in serum, but increased the level of serum testosterone in male offspring in comparison to BPA alone. Our investigations broadened the knowledge of nanotoxicity and provided important information on the safe application of CNTs.

  8. Role of taurine as a treatment for oxidative damage and sperm head abnormalities in irradiated mice and their male offspring

    El-Dawy, H.; Tawfik, S.S.; EI-Khafif, M.; Ragab, M.H.

    2007-01-01

    The efficiency of taurine therapy in treatment of male mice exposed to a dose of (3 Gy) whole body gamma irradiation and their male offspring was studied. Irradiated mice showed significant increase in plasma malonaldehyde (MDA) level and sperm head abnormality counts in all experiment interval times 1, 3 and 5 weeks. Administration of taurine (1% in drinking water) post-irradiation resulted in significant decrease in the effect of irradiation on MDA level and sperm head abnormalities count. The efficiency of taurine as radiotherapeutic agent is greatly dependent on its chemical properties as strong oxidants scavenger and biological activities as osmoregulator and membrane stabilizer. The probable mechanism of taurine was discussed, as it is a sulphydryl, heterocyclic-nitrogenous and pharmacological therapy

  9. Investigation of genomic instability by assay of DNA fingerprint from the offspring of male mice exposed to chronic low-level γ-radiation

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

    2000-01-01

    By polymerase chain reaction with arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F 1 generation) from male parents of mice exposed to chronic low-dose γ-radiation was studied. Male mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old mice progeny for DNA separation. Primer in the AP-PCR was 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on chromosome 11 of the mouse. Comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of micro-satellite-associated sequences in the genome of the offspring of males exposed to 25 and 50 cGy. DNA-fingerprints of the offspring of male mice exposed to chronic irradiation doses 10 and 25 cGy. 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of non-parent bands. Result of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-dose radiation prior to fertilization [ru

  10. Induction of external abnormalities in offspring of male mice irradiated with 252Cf neutron

    Kurishita, Akihiro; Ono, Tetsuya; Mori, Yuriko; Okada, Shigefumi; Sawada, Syozo

    1992-01-01

    To assess the genetic effects of fission neutron, the induction of external malformations was studied in F 1 fetuses after F 0 male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with 252 Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7x10 -4 /gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F 1 fetuses after spermatogonial irradiation. (author). 29 refs.; 1 fig.; 2 tabs

  11. Exposure of maternal mice to cis-bifenthrin enantioselectively disrupts the transcription of genes related to testosterone synthesis in male offspring.

    Jin, Yuanxiang; Wang, Jiangcong; Sun, Xueqing; Ye, Yang; Xu, Minjie; Wang, Jianai; Chen, Shaoping; Fu, Zhengwei

    2013-12-01

    The commercial bifenthrin (BF) contains two cis isomers. In the present study, a dose of 15mg/kg of 1R-cis-BF or 1S-cis-BF was orally administered for 3 weeks to female mice before or during pregnancy. Then, the expression of steroidogenesis related genes which were considered as effective biomarkers of endocrine disruption were analyzed in the male offspring. Maternal exposure to 1S-cis-BF during pregnancy significantly reduced the mRNA levels of peripheral benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR) in the testes of 3- or 6-week old male offspring. In addition, a significant decrease of cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α) was also observed in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during pregnancy but not before pregnancy. Moreover, the scavenger receptor class B type 1 (SRB1) and cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) decreased significantly in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during and before pregnancy. Thus, oral administration of the maternal mice to cis-BF for 3 weeks, particularly during pregnancy, resulted in endocrine disruption in the male offspring, with the 1S-cis-BF causing more significant alterations than the 1R-cis-BF form. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The effects of maternal and post-weaning diet interaction on glucose metabolism and gut microbiota in male mice offspring

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

    2016-01-01

    Substantial studies demonstrated that maternal nutrition can significantly determine the susceptibility to developing some metabolic diseases in offspring. However, investigations into the later-life effects of these diets on gut microbiota in the offspring are limited. Our objective was to explore the effects of maternal and post-weaning diet interaction on offspring's gut microbiota and glucose metabolism in later life. The male offspring of dams fed on either a high-fat (HF) diet or control (C) diet and then weaned to either a HF or C diet, generating four groups: C–C, HF–C, C–HF and HF–HF (n=8 in each group). The C–C offspring had lower body weight than C–HF group at 16 weeks of age (Pblood glucose (BG) levels of the male offspring from the C and HF dams weaned HF diet were significantly higher at 30 min, 60 min and 120 min (Pglucose administration compared with those of the C–C group. The C–HF group had higher BG at 30 min than HF–HF group (Pcurve (AUC) in C–HF and HF–HF groups was also significantly larger than C–C group (Pglucose response to a glucose load (Pglucose metabolism and alterations of gut microbiota in later life. Our study is novel in focusing on the effects of maternal and post-weaning diet interaction on offspring gut microbiota and glucose metabolism in later life. PMID:27129301

  13. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring.

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

    2017-01-01

    Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet) or a low chromium diet (LC, 0.14 mg chromium/kg diet) during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON), while others remained on the same diet (CON-CON, or LC-LC) for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA methylation which

  14. Dietary Chromium Restriction of Pregnant Mice Changes the Methylation Status of Hepatic Genes Involved with Insulin Signaling in Adult Male Offspring.

    Qian Zhang

    Full Text Available Maternal undernutrition is linked with an elevated risk of diabetes mellitus in offspring regardless of the postnatal dietary status. This is also found in maternal micro-nutrition deficiency, especial chromium which is a key glucose regulator. We investigated whether maternal chromium restriction contributes to the development of diabetes in offspring by affecting DNA methylation status in liver tissue. After being mated with control males, female weanling 8-week-old C57BL mice were fed a control diet (CON, 1.19 mg chromium/kg diet or a low chromium diet (LC, 0.14 mg chromium/kg diet during pregnancy and lactation. After weaning, some offspring were shifted to the other diet (CON-LC, or LC-CON, while others remained on the same diet (CON-CON, or LC-LC for 29 weeks. Fasting blood glucose, serum insulin, and oral glucose tolerance test was performed to evaluate the glucose metabolism condition. Methylation differences in liver from the LC-CON group and CON-CON groups were studied by using a DNA methylation array. Bisulfite sequencing was carried out to validate the results of the methylation array. Maternal chromium limitation diet increased the body weight, blood glucose, and serum insulin levels. Even when switched to the control diet after weaning, the offspring also showed impaired glucose tolerance and insulin resistance. DNA methylation profiling of the offspring livers revealed 935 differentially methylated genes in livers of the maternal chromium restriction diet group. Pathway analysis identified the insulin signaling pathway was the main process affected by hypermethylated genes. Bisulfite sequencing confirmed that some genes in insulin signaling pathway were hypermethylated in livers of the LC-CON and LC-LC group. Accordingly, the expression of genes in insulin signaling pathway was downregulated. There findings suggest that maternal chromium restriction diet results in glucose intolerance in male offspring through alterations in DNA

  15. Induction of congenital malformations in the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages

    Kirk, K.M.; Lyon, M.F.

    1984-01-01

    The induction of congenital malformations among the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages has been studied in two experiments. Firstly, animals were exposed to varying doses of X-rays and mated at various time intervals, so as to sample spermatozoa, spermatids and spermatogonial stem cells. In the second experiment, only treated spermatogonial stem cells were sampled. One group of males was given a single dose, a second group a fractionated dose and a third group was left unexposed. In the first experiment, induced post-implantation dominant lethality increased with dose, and was highest in week 3, in line with the known greater radiosensitivity of the early spermatid stage. Preimplantation loss also increased with dose and was highest in week 3. There was no clear induction of either pre-implantation or post-implantation loss at spermatogonial stem cell stages. There was a clear induction of congenital malformations at post-meiotic stages. At the two highest doses the early spermatids (15-21 days) appeared more sensitive than spermatozoa, and at this stage the incidence of malformations increased with dose. Expt. 2 showed a statistically significant induction of malformations at both dose levels. The relative sensitivities of male stem cells, post-meiotic stages and mature oocytes to the induction of congenital malformations were reasonably similar to their sensitivities for specific-locus mutations, except that the expected enhancing effect of the fractionation regime used was not seen. (Auth.)

  16. Induction of congenital malformations in the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages

    Kirk, K.M.; Lyon, M.F. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1984-01-01

    The induction of congenital malformations among the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages has been studied in two experiments. Firstly, animals were exposed to varying doses of X-rays and mated at various time intervals, so as to sample spermatozoa, spermatids and spermatogonial stem cells. In the second experiment, only treated spermatogonial stem cells were sampled. One group of males was given a single dose, a second group a fractionated dose and a third group was left unexposed. In the first experiment, induced post-implantation dominant lethality increased with dose, and was highest in week 3, in line with the known greater radiosensitivity of the early spermatid stage. Preimplantation loss also increased with dose and was highest in week 3. There was no clear induction of either pre-implantation or post-implantation loss at spermatogonial stem cell stages. There was a clear induction of congenital malformations at post-meiotic stages. At the two highest doses the early spermatids (15-21 days) appeared more sensitive than spermatozoa, and at this stage the incidence of malformations increased with dose. Expt. 2 showed a statistically significant induction of malformations at both dose levels. The relative sensitivities of male stem cells, post-meiotic stages and mature oocytes to the induction of congenital malformations were reasonably similar to their sensitivities for specific-locus mutations, except that the expected enhancing effect of the fractionation regime used was not seen.

  17. Aerobic exercise training performed by parents reduces mice offspring adiposity.

    Romero, Paulo Vitor da Silva; Guariglia, Débora Alves; Da Rocha, Francielli Ferreira; Picoli, Caroline de Carvalho; Gilio, Gustavo Renan; Fabricio, Gabriel Sergio; Mathias, Paulo Cesar de Freitas; Moraes, Solange Marta Franzói de; Peres, Sidney Barnabé

    2018-07-01

    The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

  18. Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring.

    Randy F Crossland

    Full Text Available Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP or a control protein (20% protein, C diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein and single-housed until 8-12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration, depression (tail suspension and forced swim test, sociability (three-chamber, repetitive (marble burying, learning and memory (fear conditioning, and circadian behavior (wheel-running activity during light-dark and constant dark cycles. We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT. Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03, less energy expenditure (P = 0.004, less rearing activity (P = 0.04 and a greater number of night-time rest/sleep bouts (P = 0.03 compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01 but had no learning and memory deficit in fear-conditioning assay (P = 0.02. There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces

  19. 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.

    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

  20. 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

    Alessandra Berry

    2018-03-01

    Full Text Available 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

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

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

  2. Wild-type male offspring of fmr-1+/- mothers exhibit characteristics of the fragile X phenotype.

    Zupan, Bojana; Toth, Miklos

    2008-10-01

    Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast to the expectation that wild-type (WT) males born to H (fmr-1(+/-)) mothers (H>WT) are behaviorally normal and indistinguishable from WT males born to WT mothers (WT>WT); here, we show that H>WT offspring are more active than WT>WT offspring and that their hyperactivity is similar to male KO mice born to H or KO (fmr-1(-/-)) mothers (H>KO/KO>KO). H>WT mice, however, do not exhibit seizures or abnormal sensory processing. Consistent with their hyperactivity, the effect of the D2 agonist quinpirole is reduced in H>WT as well as in H>KO and KO>KO mice compared to WT>WT offspring, suggesting a diminished feedback inhibition of dopamine release. Our data indicate that some aspects of hyperactivity and associated dopaminergic changes in 'fragile X' mice are a maternal fmr-1 genotype rather than an offspring fmr-1 genotype effect.

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

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

    2015-01-01

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

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

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

    2016-04-21

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

  5. Effects of maternal exposure to bisphenol AF on emotional behaviors in adolescent mice offspring.

    Gong, Miao; Huai, Ziqing; Song, Han; Cui, Lingyu; Guo, Qingjun; Shao, Juan; Gao, Yuan; Shi, Haishui

    2017-11-01

    Exposure to bisphenol A (BPA), one kind of environmental endocrine disruptors (EEDs), exerted significantly detrimental effects on neuro-endocrinological system and related disorders, such as memory dysfunction and depression. Bisphenol AF (BPAF),a newly introduced chemical structurally related to BPA, is used extensively. BPAF has stronger estrogenic activities than BPA. However, the potential neurotoxicological effects of BPAF are still elusive. The present study aimed to investigate the potential effects of maternal BPAF exposure during pregnancy on emotional behaviors of adolescent mice offspring. In male adolescent offspring, maternal exposure to BPAF (0.4, 4.0 mg kg -1 , intragastrically administration) induced significant anxiety- and depressive-like behaviors, assessed by open field test (OFT), novelty-suppressed feeding test (NSF), sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST). In female adolescent offspring, BPAF exposure at 0.4 mg kg -1 dose reduced the latency to feeding in the NSF test, while increased the floating time in the FST. Maternal BPAF exposure decreased the recognition index in the long term memory (LTM) test in both sexes, while only decreased the freezing time of male offspring in the contextual fear conditioning (CFC) task. These results indicate that maternal exposure to BPAF significantly affect emotion-related behaviors in adolescent mice offspring, and the male offspring with a higher probability to develop symptoms of anxiety and depression and to suffer memory impairment after maternal exposure to BPAF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Effects of ethanol on offspring of C57BL/6J mice alcoholized during gestation

    Grinfeld Hermann

    1999-01-01

    Full Text Available The effects of chronic alcohol consumption during pregnancy were analysed in the gestation and offspring of alcoholized mice. Female C57BL/6J mice were placed overnight with stud males and the presence of a sperm plug in the next morning indicated the onset of gestation. Pregnant mice were distributed in two weight-matched groups. In the alcoholized group, the mice received a high protein liquid diet ad libitum containing 27.5% of ethanol-derived calories (5.28% v/v from gestation day 5 to 19. The control group received the same volume of diet containing isocaloric amounts of maltose-dextrin substituted for ethanol. After postnatal day zero, the dams received food pellets and tap water ad libitum. On postnatal day 6 the pups were counted and weighed at variable intervals up to the 60th day of life. The majority of the pregnant dams that have received ethanol completed the gestational period, and the chronic consumption of alcohol did not interfere with the number of dams that gave birth. The alcoholized and control dams gained an equivalent weight and consumed an equivalent volume of diet throughout the gestation. The number of pups from alcohol diet dams was 46,26% smaller compared with the control group. There were less male than female pups in the offspring of alcoholized mice. Teratogeny like gastroschisis and limb malformation were present in the offspring of alcoholized dams. The body weight of the offspring of alcoholized mice increased from the 18th to the 36th postnatal day.

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

    AbuTaweel Qasim M; Ajarem Jamaan S

    2008-01-01

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

  8. HY immune tolerance is common in women without male offspring.

    Miranda P Dierselhuis

    Full Text Available Sex difference is an established risk factor for hematopoietic stem cell transplantation (HSCT-related complications like graft versus host disease (GVHD. CD8pos cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens (HY play an important role therein. Prior to HSC donation, female donors may encounter HY antigens through fetomaternal or transmaternal cell flow, potentially leading to the induction of HY-specific cytotoxic or regulatory immune responses. Whether HY priming occurs independent of parity, and whether HY priming is dependent on the presence of male microchimerism, is as yet unknown.We investigated the presence of HY-specific regulatory T cells (Treg and male microchimerism in 45 healthy women with a fully documented pregnancy and family history. HY peptide-induced linked suppression, a commonly reported functional feature of CD4pos and CD8pos Treg, was measured by trans vivo Delayed Type Hypersensitivity testing. As source of HY antigens, male microchimerism was analyzed by real-time PCR and defined by the presence of male DNA in at least one purified leukocyte cell type.HLA class I or class II restricted HY-specific Treg were detected in 26/42 (62% women eligible for analysis. The prevalence of HY-specific Treg was significantly higher in women who had never given birth to sons than in women with male offspring (p = 0.004. Male microchimerism could be detected in 24 out of 45 (53% women but did not correlate with the presence of HY specific Treg.HY-specific Treg in women with male offspring have been described previously. Here we show for the first time that, in fact, HY specific Treg are more common in nulliparous women and in parous women with female offspring. Their presence is independent of the presence of male microchimerism. Whether HY-specific Treg presence in female stem cell grafts might decrease the GVHD incidence in male HSCT recipients needs to be investigated.

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

    Claire J Foldi

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

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

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

    2017-07-01

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

  11. Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy.

    Oelkrug, Rebecca; Herrmann, Beate; Geissler, Cathleen; Harder, Lisbeth; Koch, Christiane; Lehnert, Hendrik; Oster, Henrik; Kirchner, Henriette; Mittag, Jens

    2017-10-01

    Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments. We sought to test the consequences of maternal α1-adrenergic antagonism during pregnancy, which can occur e.g. during hypertension treatment, for the endocrine and metabolic phenotype of the offspring. We treated C57BL/6NCrl female mice with the α1-adrenergic antagonist prazosin during pregnancy and analyzed the male and female offspring for endocrine and metabolic abnormalities. Our data revealed that maternal α1-adrenergic blockade caused dwarfism, elevated body temperature, and insulin resistance in male offspring, accompanied by reduced IGF-1 serum concentrations as the result of reduced hepatic growth hormone receptor (Ghr) expression. We subsequently identified increased CpG DNA methylation at the transcriptional start site of the alternative Ghr promotor caused by the maternal treatment, which showed a strong inverse correlation to hepatic Ghr expression. Our results demonstrate that maternal α1-adrenergic blockade can constitute an epigenetic cause for dwarfism and insulin resistance. The findings are of immediate clinical relevance as combined α/β-adrenergic blockers are first-line treatment of maternal hypertension. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

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

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

    2015-02-01

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

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

    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.

  14. Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR γ methylation in offspring, grand-offspring mice.

    Zhonghai Yan

    Full Text Available Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear.We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected.Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR γ, CCAAT/enhancer-binding proteins (C/EBP α, cyclooxygenase (Cox-2, fatty acid synthase (FAS and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue.Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice.Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.

  15. Will male advertisement be a reliable indicator of paternal care, if offspring survival depends on male care?

    Kelly, Natasha B.; Alonzo, Suzanne H.

    2009-01-01

    Existing theory predicts that male signalling can be an unreliable indicator of paternal care, but assumes that males with high levels of mating success can have high current reproductive success, without providing any parental care. As a result, this theory does not hold for the many species where offspring survival depends on male parental care. We modelled male allocation of resources between advertisement and care for species with male care where males vary in quality, and the effect of c...

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

    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.

  17. Proteomic Analysis of Pachytene Spermatocytes of Sterile Hybrid Male Mice.

    Wang, Lu; Guo, Yueshuai; Liu, Wenjing; Zhao, Weidong; Song, Gendi; Zhou, Tao; Huang, Hefeng; Guo, Xuejiang; Sun, Fei

    2016-09-01

    Incompatibilities in interspecific hybrids, such as reduced hybrid fertility and lethality, are common features resulting from reproductive isolation that lead to speciation. Subspecies crosses of house mice produce offspring in which one sex is infertile or absent, yet the molecular mechanisms of hybrid sterility are poorly understood. In this study, we observed extensive asynapsis of chromosomes and disturbance of the sex body in pachytene spermatocytes of sterile F1 males (PWK/Ph female × C57BL/6J male). We report the high-confidence identification of 4005 proteins in the pachytene spermatocytes of fertile F1 males (PWK/Ph male × C57BL/6J female) and sterile F1 males (PWK/Ph female × C57BL/6J male), of which 215 were upregulated and 381 were downregulated. Bioinformatics analysis of the proteome led to the identification of 43 and 59 proteins known to be essential for male meiosis and spermatogenesis in mice, respectively. Characterization of the proteome of pachytene spermatocytes associated with hybrid male sterility provides an inventory of proteins that is useful for understanding meiosis and the mechanisms of hybrid male infertility. © 2016 by the Society for the Study of Reproduction, Inc.

  18. High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

    Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

    2015-07-17

    This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

  19. Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring

    Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A.; Carter, Anthony J.

    2016-01-01

    Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

  20. Photoperiodism of Male Offspring Production in the Water Flea Daphnia pulex.

    Toyota, Kenji; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

    2017-08-01

    Photoperiodism is a biological seasonal timing system utilized to regulate development and reproduction in organisms. The freshwater micro-crustacean Daphnia pulex displays environmental sex determination, the precise physiological mechanisms of which are largely unknown due to the lack of an experimental system to induce female or male offspring production by alterations of the rearing environment. We recently found that D. pulex, WTN6 strain, produces female or male offspring in response to long-day or short-day conditions, respectively. Taking advantage of this system, here we report the photoperiodic response curve for male offspring production, showing 12 hours as natural critical daylength (50% incidence of male-producing mothers), and that male offspring inducibility is highly sensitive to photoperiodic alterations. By using monochromatic light emitting diode (LED) devices, we found that the effective wavelength is red-light (627 nm), which stably induces male offspring production. This suggests that the red-light photoreceptor may be decisive in the primary step of sex determination process in this strain. Our findings provide the first insights into photoperiodism and red-light as key factors in triggering male offspring production in daphnids.

  1. Will male advertisement be a reliable indicator of paternal care, if offspring survival depends on male care?

    Kelly, Natasha B; Alonzo, Suzanne H

    2009-09-07

    Existing theory predicts that male signalling can be an unreliable indicator of paternal care, but assumes that males with high levels of mating success can have high current reproductive success, without providing any parental care. As a result, this theory does not hold for the many species where offspring survival depends on male parental care. We modelled male allocation of resources between advertisement and care for species with male care where males vary in quality, and the effect of care and advertisement on male fitness is multiplicative rather than additive. Our model predicts that males will allocate proportionally more of their resources to whichever trait (advertisement or paternal care) is more fitness limiting. In contrast to previous theory, we find that male advertisement is always a reliable indicator of paternal care and male phenotypic quality (e.g. males with higher levels of advertisement never allocate less to care than males with lower levels of advertisement). Our model shows that the predicted pattern of male allocation and the reliability of male signalling depend very strongly on whether paternal care is assumed to be necessary for offspring survival and how male care affects offspring survival and male fitness.

  2. Paternal spatial training enhances offspring's cognitive performance and synaptic plasticity in wild-type but not improve memory deficit in Alzheimer's mice.

    Zhang, Shujuan; Li, Xiaoguang; Wang, Zhouyi; Liu, Yanchao; Gao, Yuan; Tan, Lu; Liu, Enjie; Zhou, Qiuzhi; Xu, Cheng; Wang, Xin; Liu, Gongping; Chen, Haote; Wang, Jian-Zhi

    2017-05-08

    Recent studies suggest that spatial training can maintain associative memory capacity in Tg2576 mice, but it is not known whether the beneficial effects can be inherited from the trained fathers to their offspring. Here, we exposed male wild-type and male 3XTg Alzheimer disease (AD) mice (3-m old) respectively to spatial training for one week and assessed the transgenerational effects in the F1 offspring when they were grown to 7-m old. We found that the paternal spatial training significantly enhanced progeny's spatial cognitive performance and synaptic transmission in wild-type mice. Among several synapse- or memory-associated proteins, we observed that the expression level of synaptotagmin 1 (SYT1) was significantly increased in the hippocampus of the paternally trained-offspring. Paternal training increased histone acetylation at the promoter of SYT1 in both fathers' and the offspring's hippocampus, and as well as in the fathers' sperm. Finally, paternal spatial training for one week did not improve memory and synaptic plasticity in 3XTg AD F1 offspring. Our findings suggest paternal spatial training for one week benefits the offspring's cognitive performance in wild-type mice with the mechanisms involving an enhanced transgenerational histone acetylation at SYT1 promoter.

  3. Male mice ultrasonic vocalizations enhance female sexual approach and hypothalamic kisspeptin neuron activity.

    Asaba, Akari; Osakada, Takuya; Touhara, Kazushige; Kato, Masahiro; Mogi, Kazutaka; Kikusui, Takefumi

    2017-08-01

    Vocal communication in animals is important for ensuring reproductive success. Male mice emit song-like "ultrasonic vocalizations (USVs)" when they encounter female mice, and females show approach to the USVs. However, it is unclear whether USVs of male mice trigger female behavioral and endocrine responses in reproduction. In this study, we first investigated the relationship between the number of deliveries in breeding pairs for 4months and USVs syllables emitted from those paired males during 3min of sexual encounter with unfamiliar female mice. There was a positive correlation between these two indices, which suggests that breeding pairs in which males could emit USVs more frequently had more offspring. Further, we examined the effect of USVs of male mice on female sexual behavior. Female mice showed more approach behavior towards vocalizing males than devocalized males. Finally, to determine whether USVs of male mice could activate the neural system governing reproductive function in female mice, the activation of kisspeptin neurons, key neurons to drive gonadotropin-releasing hormone neurons in the hypothalamus, was examined using dual-label immunocytochemistry with cAMP response element-binding protein phosphorylation (pCREB). In the arcuate nucleus (Arc), the number of kisspeptin neurons expressing pCREB significantly increased after exposure to USVs of male as compared with noise exposure group. In conclusion, our results suggest that USVs of male mice promote fertility in female mice by activating both their approaching behavior and central kisspeptin neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. What effects can be expected of prenatal ethanol exposure in pregnant mice and their offspring?

    Hermann Grinfeld

    2004-09-01

    Full Text Available Objective: To investigate the effects of chronic alcohol consumptionin pregnant mice and their offspring. Methods: Twenty eight femaleC57BL/6J pregnant mice were distributed in two weight-matchedgroups. One group received a high protein ad libitum liquid dietcontaining 27.5% of ethanol-derived calories, from gestation day 5to 19. The control group received the same volume of diet containingisocaloric amounts of maltose-dextrin. On postnatal day 6 thepups were counted and weighed at variable intervals up to the60th day of life. On postnatal day 60, the males of the two groups(control and ethanol were randomly assigned into 4 subgroupswhich were injected subcutaneously either with neurotoxin 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine or vehicle control.Seven days after the injection the subjects were weighed,sacrificed, and their brains were removed and processed forimmunohistochemistry and neuronal counting by stereologicalmethods. Results: The number of pups from the ethanol dietmothers was significantly smaller compared with the control group(3.54 ± 0.45 and 6.5 ± 0.42 respectively; p < 0.01, in addition ofincreased neonatal mortality and teratogeny, like gastroschisis.Decreased number of pups was observed among the male offspringof the ethanol diet mothers (1.54 ± 0.31 and 2.87 ± 0.48; p < 0.05.The brains of the ethanol diet group that received either the toxinor solvent showed a significantly decreased number ofdopaminergic neurons in the pars compacta of substantia nigra asrelated to the control group that received the solvent. An increasednumber of reactive astrocytes was observed in the striatum ofsubjects of the alcohol/diet group injected with the toxin.Conclusions: Data showed that gestational alcoholism has animportant role in teratogeny as well as modifying the nigrostriataldopaminergic system of the mice offspring.

  5. Metabolic and affective consequences of fatherhood in male California mice.

    Zhao, Meng; Garland, Theodore; Chappell, Mark A; Andrew, Jacob R; Saltzman, Wendy

    2017-08-01

    Physiological and affective condition can be modulated by the social environment and parental state in mammals. However, in species in which males assist with rearing offspring, the metabolic and affective effects of pair bonding and fatherhood on males have rarely been explored. In this study we tested the hypothesis that fathers, like mothers, experience energetic costs as well as behavioral and affective changes (e.g., depression, anxiety) associated with parenthood. We tested this hypothesis in the monogamous, biparental California mouse (Peromyscus californicus). Food intake, blood glucose and lipid levels, blood insulin and leptin levels, body composition, pain sensitivity, and depression-like behavior were compared in males from three reproductive groups: virgin males (VM, housed with another male), non-breeding males (NB, housed with a tubally ligated female), and breeding males (BM, housed with a female and their first litter). We found statistically significant (Pfatherhood influences several metabolic, morphological, and affective measures in male California mice. Overall, the changes we observed in breeding males were minor, but stronger effects might occur in long-term breeding males and/or under more challenging environmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Effects of fetal microwave radiation exposure on offspring behavior in mice

    Zhang Yanchun; Li Zhihui; Gao Yan; Zhang Chenggang

    2015-01-01

    The recent rapid development of electronic communication techniques is resulting in a marked increase in exposure of humans to electromagnetic fields (EMFs). This has raised public concerns about the health hazards of long-term environmental EMF exposure for fetuses and children. Some studies have suggested EMF exposure in children could induce nervous system disorders. However, gender-dependent effects of microwave radiation exposure on cognitive dysfunction have not previously been reported. Here we investigated whether in utero exposure to 9.417-GHz microwave throughout gestation (Days 3.5–18) affected behavior, using the open field test (OFT), elevated-plus maze (EPM), tail suspension test (TST), forced swimming test (FST) and Morris water maze (MWM). We found that mice showed less movement in the center of an open field (using the OFT) and in an open arm (using the EPM) after in utero exposure to 9.417-GHz radiation, which suggested that the mice had increased anxiety-related behavior. Mice demonstrated reduced immobility in TST and FST after in utero exposure to 9.417-GHz radiation, which suggested that the mice had decreased depression-related behavior. From the MWM test, we observed that male offspring demonstrated decreased learning and memory, while females were not affected in learning and memory, which suggested that microwaves had gender-dependent effects. In summary, we have provided the first experimental evidence of microwaves inducing gender-dependent effects. (author)

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

    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.

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

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

    2017-07-01

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

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

    Yifan Huang

    2014-04-01

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

  10. Prenatal Metformin Exposure in Mice Programs the Metabolic Phenotype of the Offspring during a High Fat Diet at Adulthood

    Salomäki, Henriikka; Vähätalo, Laura H.; Laurila, Kirsti; Jäppinen, Norma T.; Penttinen, Anna-Maija; Ailanen, Liisa; Ilyasizadeh, Juan; Pesonen, Ullamari; Koulu, Markku

    2013-01-01

    Aims The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. Methods Metformin (300 mg/kg) or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase) and high fat diet (HFD-phase). At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. Results Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. Conclusions The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a therapeutic agent during

  11. Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood.

    Henriikka Salomäki

    Full Text Available AIMS: The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. METHODS: Metformin (300 mg/kg or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase and high fat diet (HFD-phase. At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. RESULTS: Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. CONCLUSIONS: The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a

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

    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

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

    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.

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

    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.

  15. Nutritional Programming of Bone Structure in Male Offspring by Maternal Consumption of Citrus Flavanones.

    Sacco, Sandra M; Saint, Caitlin; LeBlanc, Paul J; Ward, Wendy E

    2018-06-01

    Maternal exposure to hesperidin (HSP) and naringin (NAR) during pregnancy and lactation transiently compromised bone mineral density (BMD) and bone structure at the proximal tibia in female CD-1 offspring. We examined whether maternal consumption of HSP + NAR during pregnancy and lactation compromises BMD, bone structure, and bone strength in male CD-1 offspring. Male CD-1 offspring, from mothers fed a control diet (CON, n = 10) or a 0.5% HSP + 0.25% NAR diet (HSP + NAR, n = 8) for 5 weeks before mating and throughout pregnancy and lactation, were weaned and fed CON until 6 months of age. In vivo micro-computed tomography (µCT) measured tibia BMD and structure at 2, 4, and 6 months of age. Ex vivo µCT measured femur and lumbar vertebrae (LV) structure at age 6 months. Ex vivo BMD (femur, LV) and biomechanical strength (femur and tibia midpoint, femur neck) were assessed at age 6 months by dual energy x-ray absorptiometry and strength testing, respectively. At all ages, HSP + NAR offspring had greater (p structure compared to CON offspring. At age 4 months, proximal tibia trabecular structure was greater (p structure were greater (p structure at the proximal tibia in male CD-1 offspring that persisted to 6 months of age. Thus, maternal programming of offspring BMD and bone structure from consumption of HSP + NAR occurred as a sex-specific response.

  16. Male rank affects reproductive success and offspring performance in bank voles.

    Kruczek, Małgorzata; Zatorska, Magdalena

    2008-07-05

    Laboratory studies reveal that in several rodent species the females prefer dominant males as mating partners. Here we investigate the correlation between males' social rank and their reproductive success. Similar numbers of females mating with relatively more dominant or relatively more subordinate males produced a litter, and parturition took place 19-21 days after mating. Relatively more dominant males tended to sire more pups than did relatively more subordinates, but the mean number of offspring per litter did not differ significantly between the two groups. Significantly more pups fathered by relatively more dominant males survived to weaning than those sired by relatively more subordinate fathers. Dominance had a long-term effect on the reproductive activity of the offspring: their rate of sexual maturation was increased. In pups sired by a relatively more dominant father, the uteruses of females, and the testes and accessory sex glands of males, were significantly heavier than those of offspring born to relatively more subordinate males. Our results suggest that social rank is an important determinant of the reproductive success of bank vole males.

  17. Prenatal exposure to antifungal medication may change anogenital distance in male offspring

    Madelung Mogensen, Djamilla; Bergkvist Pihl, Maria; Skakkebæk, Niels E.

    2017-01-01

    BACKGROUND: Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is associated with a shorter (less masculine) anogenital distance (AGD) in male offspring. To our...

  18. Prenatal exposure to antifungal medication may change anogenital distance in male offspring

    Mogensen, Djamilla Madelung; Pihl, Maria Bergkvist; Skakkebæk, Niels Erik

    2017-01-01

    (AGDap) and penile width; measured at the base of the penis. Results: Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21...

  19. Prenatally administered HMB modifies the enamel surface roughness in spiny mice offspring: An atomic force microscopy study.

    Świetlicka, Izabela; Muszyński, Siemowit; Tomaszewska, Ewa; Dobrowolski, Piotr; Kwaśniewska, Anita; Świetlicki, Michał; Skic, Anna; Gołacki, Krzysztof

    2016-10-01

    The aim of this research was to check the effect of the prenatally administered β-hydroxy β-methylbutyrate (HMB) on the development of enamel surface of the spiny mice offspring. The spiny mice dams were randomly assigned into three groups: control group (not supplemented with HMB) and two experimental groups in which powdered HMB was given at the daily dosage of 0.2g/kg of body weight (group I) and 0.02g/kg of body weight (group II) during the last period of gestation. Newborn pups were euthanized by CO 2 inhalation. The morphology of incisor teeth was analysed using atomic force microscopy (AFM) in semi-contact mode in the height, magnitude and phase domains. Height images became a basis for determination of surface roughness parameters. Conducted study indicated that maternal HMB administration markedly influences enamel development. Enamel of offspring's teeth in both experimental groups was characterized by significantly smaller values of indices describing surface roughness and profile. HMB supplementation influenced the calculated parameters regardless of the diet type and offspring sex, however higher dose of HMB caused stronger changes in enamel surface's physical properties and could be observed in higher intensity in the male group. HMB administration caused reduction in the irregularities of enamel surface, thereby possibly reducing the probability of bacteria adhesion and caries development. These observations may serve to improve nutrition and supplementation of animals and could be a lead for further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Morphometric variables of offspring of Quassia amara treated male ...

    Reproductive toxicological action of Q. amara is well documented but no information exists on its effect on prenatal programming. Methods: Adult male rats (180-200g, n=5) were treated daily (p.o) with Q. amara extract (100 mg/kg) for 6 weeks. A control group received distilled water. After 5 weeks of treatment, female rats ...

  1. Born in an alien nest: how do social parasite male offspring escape from host aggression?

    Patrick Lhomme

    Full Text Available Social parasites exploit the colony resources of social insects. Some of them exploit the host colony as a food resource or as a shelter whereas other species also exploit the brood care behavior of their social host. Some of these species have even lost the worker caste and rely completely on the host's worker force to rear their offspring. To avoid host defenses and bypass their recognition code, these social parasites have developed several sophisticated chemical infiltration strategies. These infiltration strategies have been highly studied in several hymenopterans. Once a social parasite has successfully entered a host nest and integrated its social system, its emerging offspring still face the same challenge of avoiding host recognition. However, the strategy used by the offspring to survive within the host nest without being killed is still poorly documented. In cuckoo bumblebees, the parasite males completely lack the morphological and chemical adaptations to social parasitism that the females possess. Moreover, young parasite males exhibit an early production of species-specific cephalic secretions, used as sexual pheromones. Host workers might thus be able to recognize them. Here we used a bumblebee host-social parasite system to test the hypothesis that social parasite male offspring exhibit a chemical defense strategy to escape from host aggression during their intranidal life. Using behavioral assays, we showed that extracts from the heads of young cuckoo bumblebee males contain a repellent odor that prevents parasite males from being attacked by host workers. We also show that social parasitism reduces host worker aggressiveness and helps parasite offspring acceptance.

  2. Influence of paternal 252Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F1 offspring of mice

    Watanabe, Hiromitsu; Takahashi, Tadateru; Lee, Juing-Yi

    1996-01-01

    Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with 252 Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P 1 generation may be caused by genetic transmission of hepatoma-associated trait (s) induced by 252 Cf neutron irradiation. (author)

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

    Lee O'Sullivan

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

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

    Abbasali Gaeini

    2016-05-01

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

  5. Exposure to Alumina Nanoparticles in Female Mice During Pregnancy Induces Neurodevelopmental Toxicity in the Offspring.

    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.

  6. Paternal preconception alcohol exposure imparts intergenerational alcohol-related behaviors to male offspring on a pure C57BL/6J background.

    Rompala, Gregory R; Finegersh, Andrey; Slater, Michelle; Homanics, Gregg E

    2017-05-01

    While alcohol use disorder (AUD) is a highly heritable condition, the basis of AUD in families with a history of alcoholism is difficult to explain by genetic variation alone. Emerging evidence suggests that parental experience prior to conception can affect inheritance of complex behaviors in offspring via non-genomic (epigenetic) mechanisms. For instance, male C57BL/6J (B6) mice exposed to chronic intermittent vapor ethanol (CIE) prior to mating with Strain 129S1/SvImJ ethanol-naïve females produce male offspring with reduced ethanol-drinking preference, increased ethanol sensitivity, and increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). In the present study, we tested the hypothesis that these intergenerational effects of paternal CIE are reproducible in male offspring on an inbred B6 background. To this end, B6 males were exposed to 6 weeks of CIE (or room air as a control) before mating with ethanol-naïve B6 females to produce ethanol (E)-sired and control (C)-sired male and female offspring. We observed a sex-specific effect, as E-sired males exhibited decreased two-bottle free-choice ethanol-drinking preference, increased sensitivity to the anxiolytic effects of ethanol, and increased VTA BDNF expression; no differences were observed in female offspring. These findings confirm and extend our previous results by demonstrating that the effects of paternal preconception ethanol are reproducible using genetically identical, inbred B6 animals. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effect of Soybean on Male Reproductive Physiology in Male Mice

    M Modaresi

    2011-01-01

    Full Text Available Introduction & Objective: Soybean (Soja hispida Moench is a member of Fabaceae family. It is a species of legume native to East Asia. Soy contains significant amount of all the essential amino acids for humans therefore, is a good source of protein .Soy has an important role in the improvement and treatment of some cancers such as colon, prostate, and breast. The aim of this study was to investigate the effect of soybeans on reproductive system in male mice. Materials & Methods: This experimental study was conducted at Isfahan Payam e Noor University in 2009. In this research, 32 male mice were randomly grouped into four experimental groups. The control group was fed with soy-free basic diet. The experimental groups 1, 2, and 3 were fed with a diet containing 20%, 30% and 50% soy diet respectively.At the end of 9 weeks of treatment, blood samples were collected and serum levels of testosterone, LH and FSH were measured. The collected data was analyzed with SPSS software using one way ANOVA with Dunnett's post test and Duncan test. Results : In the experimental group which received 20% soy diet, the level of testosterone had a meaningful decrease in comparison with the control group (P<0.05, but in the experimental group which received a 50% soy diet, the level of testosterone had a meaningful increase (P<0.05 .The LH level in 30% and 50% groups had a meaningful increase but no significant differences were observed in FSH level & weight of testicles (P<0.05.The number of sperms in all of the treatment regimes had a meaningful decrease (P0.05 Conclusion: Results of this research indicated that the 20, 30, and 50 percent soy diet had a negative effect on the male reproductive system in mice.

  8. Subordinate Males Sire Offspring in Madagascar Fish-eagle (Haliaeetus Vociferoides) Polyandrous Breeding Groups

    Tingay, Ruth E.; Culver, Melanie; Hallerman, Eric M.; Fraser, James D.; Watson, Richard T.

    2002-01-01

    The island endemic Madagascar Fish-Eagle (Haliaeetus vociferoides) is one of the most endangered birds of prey. Certain populations in west-central Madagascar sometimes exhibit a third, and sometimes a fourth, adult involved in breeding activities at a nest. We applied DNA fingerprinting to assess relatedness among 17 individuals at four nests. In all nests with young, a subordinate rather than the dominant male sired the offspring. Within-nest relatedness comparisons showed that some dominan...

  9. Should attractive males sneak: the trade-off between current and future offspring.

    Ulrika Candolin

    Full Text Available Alternative reproductive tactics are predicted to be adopted by less competitive males when competition for fertilization is intense. Yet, in some species, competitively superior males use an alternative tactic alongside the conventional tactic. This can jeopardize their success through the conventional tactic, but surprisingly little attention has been paid to this cost. We investigated 1 the degree to which competitive males sneak fertilize eggs in the polygamous threespine stickleback, Gasterosteus aculeatus, and 2 if males balance the cost of sneaking against its benefit. We found competitive males that succeeded in establishing a territory and in attracting spawning females to perform most sneak fertilizations. However, when we reduced the benefit of sneak attempts, by reducing visibility and the success rate of sneak attempts, males sneaked less. When we increased the cost of sneak attempts, by increasing the perceived value of current offspring (by mating males to preferred females rather than unpreferred females or no females, the interest of males in sneak opportunities decreased. Intriguingly, larger males, who presumably had a higher probability of future reproduction, were more willing to risk their current offspring for sneak opportunities. These findings suggest that competitive males that are attractive to females carefully balance costs against benefits in their sneaking decisions. More broadly, our results imply that changes in the environment can influence the cost-benefit ratio of sneaking and alter the distribution of fertilizations in a population. We end with discussing the implications that alterations in sneaking behavior could have for the operation of sexual selection in changing environments.

  10. Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring

    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...

  11. Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring.

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

    2017-08-01

    Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.

  12. Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.

    Kim, Juyoung; Kim, Juhae; Kwon, Young Hye

    2016-08-01

    Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including LXRα, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

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

    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.

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

    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

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

    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.

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

    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

  17. Hepatic peroxisome proliferator-activated receptor α may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice

    Hayashi, Yumi; Ito, Yuki; Yamagishi, Nozomi; Yanagiba, Yukie; Tamada, Hazuki; Wang, Dong; Ramdhan, Doni Hikmat; Naito, Hisao; Harada, Yukiko; Kamijima, Michihiro; Gonzales, Frank J.; Nakajima, Tamie

    2011-01-01

    Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with adverse effects on offspring, and the metabolites are agonists of peroxisome proliferator-activated receptor (PPAR) α, which exhibits species differences in expression and function. This study aimed to clarify the mechanism of DEHP-induced adverse effects on offspring in relation to maternal mouse and human PPARα. Male and female Sv/129 wild-type (mPPARα), Pparα-null and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% (medium) or 0.1% (high) DEHP. After 4 weeks, males and females were mated. Dams were killed on gestational day 18 and postnatal day (PND) 2. High-dose DEHP decreased the number of total and live fetuses, and increased resorptions in mPPARα mice. In hPPARα mice, resorptions were increased above the medium dose, and the number of births was decreased at the high dose. The number of live pups on PND2 was decreased over the medium dose in mPPARα and at the high dose in hPPARα mice. No such findings were observed in Pparα-null mice. High-dose DEHP decreased plasma triglyceride in pregnant mPPARα mice, but not in Pparα-null and hPPARα ones. Above the medium dose in mPPARα mice significantly reduced hepatic microsomal triglyceride transfer protein (MTP) expression. Medium- and/or high-dose DEHP increased the levels of maternal PPARα target genes in mPPARα and hPPARα mice. Taken together, PPARα expression is required for the toxicity of DEHP in fetuses and pups and altered plasma triglyceride levels, through regulation of MTP may be important in mPPARα mice and not in hPPARα mice.

  18. A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

    Michael Kruse

    2017-07-01

    Full Text Available Background/Aims: Altered nutrients during the in utero (IU and/or lactation (L period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT mice were fed either a HFD or control chow (C prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT1- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.

  19. Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

    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.

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

    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.

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

    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

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

    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.

  3. Do male desert gobies compromise offspring care to attract additional mating opportunities?

    Nicholas Symons

    Full Text Available Males often play a critical role in offspring care but the time and energy invested in looking after young can potentially limit their ability to seek out additional mating opportunities. Recent studies, however, suggest that a conflict between male parental effort and mating effort may not always be inevitable, especially if breeding occurs near the nest, or if parental behaviours are under sexual selection. Accordingly, we set out to experimentally investigate male care and courtship in the desert goby Chlamydogobius eremius, a nest-guarding fish with exclusive paternal care. Despite courtship occurring near the nest, we found that when egg-tending males were given the opportunity to attract additional females, they fanned their eggs less often, engaged in shorter fanning bouts, and spent more of their time outside their nests courting. Our findings highlight the importance of understanding the circumstances under which reproductive tradeoffs are expected to occur and how these, in turn, operate to influence male reproductive decisions.

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

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

    2014-01-01

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

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

    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.

  6. Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.

    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.

  7. Retardation of muscle growth in castrated male mice: further ...

    Retardation of muscle growth in castrated male mice was studied as an evidence for the influence of hormones on the development of muscle mass. Male albino mice were castrated at 28days of age by open castration method. The weights and the muscle mass indices (mg muscle weight per gram body weight) of the ...

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

    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.

  9. Egg Speckling Patterns Do Not Advertise Offspring Quality or Influence Male Provisioning in Great Tits

    Stoddard, Mary Caswell; Fayet, Annette L.; Kilner, Rebecca M.; Hinde, Camilla A.

    2012-01-01

    Many passerine birds lay white eggs with reddish brown speckles produced by protoporphyrin pigment. However, the function of these spots is contested. Recently, the sexually selected eggshell coloration (SSEC) hypothesis proposed that eggshell color is a sexually selected signal through which a female advertises her quality (and hence the potential quality of her future young) to her male partner, thereby encouraging him to contribute more to breeding attempts. We performed a test of the SSEC hypothesis in a common passerine, the great tit Parus major. We used a double cross-fostering design to determine whether males change their provisioning behavior based on eggshell patterns they observe at the nest. We also tested the assumption that egg patterning reflects female and/or offspring quality. Because birds differ from humans in their color and pattern perception, we used digital photography and models of bird vision to quantify egg patterns objectively. Neither male provisioning nor chick growth was related to the pattern of eggs males observed during incubation. Although heavy females laid paler, less speckled eggs, these eggs did not produce chicks that grew faster. Therefore, we conclude that the SSEC hypothesis is an unlikely explanation for the evolution of egg speckling in great tits. PMID:22815730

  10. Egg speckling patterns do not advertise offspring quality or influence male provisioning in great tits.

    Mary Caswell Stoddard

    Full Text Available Many passerine birds lay white eggs with reddish brown speckles produced by protoporphyrin pigment. However, the function of these spots is contested. Recently, the sexually selected eggshell coloration (SSEC hypothesis proposed that eggshell color is a sexually selected signal through which a female advertises her quality (and hence the potential quality of her future young to her male partner, thereby encouraging him to contribute more to breeding attempts. We performed a test of the SSEC hypothesis in a common passerine, the great tit Parus major. We used a double cross-fostering design to determine whether males change their provisioning behavior based on eggshell patterns they observe at the nest. We also tested the assumption that egg patterning reflects female and/or offspring quality. Because birds differ from humans in their color and pattern perception, we used digital photography and models of bird vision to quantify egg patterns objectively. Neither male provisioning nor chick growth was related to the pattern of eggs males observed during incubation. Although heavy females laid paler, less speckled eggs, these eggs did not produce chicks that grew faster. Therefore, we conclude that the SSEC hypothesis is an unlikely explanation for the evolution of egg speckling in great tits.

  11. Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.

    Rompala, Gregory R; Finegersh, Andrey; Homanics, Gregg E

    2016-06-01

    A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. [Perinatal clomiphene citrate treatment changes sexual orientations of male mice].

    He, Feng-Qin; Zhang, Heng-Rui

    2013-10-01

    Perinatal period and adolescence are critical for brain development, which is the biological basis of an individual's sexual orientation and sexual behavior. In this study, animals were divided into two groups and their sexual orientations were observed: one group experienced drug treatments during the perinatal period, and the other group was castrated at puberty. The results showed that estradiol treatment had no effect on mature male offspring's sexual orientations, but 9 days and 14 days of clomiphene citrate treatment significantly increased the chance of homosexuality and effeminized behavior. In addition, the sexual orientation of mature normal male offspring, which were castrated when they were 21 days old,was not significant different from the control animals. These findings suggest that the inhibition of perinatal estrogen activities could suppress individual male-typical responses, enhance female-typical responses and induce homosexual orientations. Moreover, the masculinizing effects of estrogen were more obvious during perinatal period than adolescence.

  13. Maternal exposure to airborne particulate matter causes postnatal immunological dysfunction in mice offspring

    Hong, Xinru; Liu, Chaobin; Chen, Xiaoqiu; Song, Yanfeng; Wang, Qin; Wang, Ping; Hu, Dian

    2013-01-01

    Evidence suggests that prenatal exposure to air pollution affects the ontogeny and development of the fetal immune system. The aim of this study was to investigate the effect of maternal exposure to airborne particulate matter (PM) on immune function in postnatal offspring. Pregnant female ICR mice were intralaryngopharyngeally administered with 30 μl of phosphate buffered solution (the control group) or resuspended PM of Standard Reference Material 1649a at 0.09 (low), 0.28 (medium), 1.85 (high) or 6.92 (overdose) μg/μl once every three days from day 0 to 18 of pregnancy (n = 8–10). Offspring were sacrificed on postnatal day 30. Interleukin-4 and interferon-γ levels in plasma and splenocytes, splenic lymphocyte proliferation, and expressions of GATA-3 and T-bet mRNA in the spleen were tested. The spleen and thymus were histopathologically examined. The offspring of the medium, high and overdose PM-exposed dams showed significantly suppressed splenocyte proliferation. Decreased interferon-γ and increased interleukin-4 levels in the blood and splenocytes, and lowered T-bet and elevated GATA-3 mRNA expressions were found in the spleen in the medium, high and overdose groups when compared with the control or low dose group (P < 0.05). Histopathology revealed prominent tissue damage in the spleen and thymus in the overdose group. These results suggest that exposure of pregnant mice to PM modulates the fetal immune system, resulting in postnatal immune dysfunction by exacerbation of Thl/Th2 deviation. This deviation is associated with altered T-bet and GATA-3 gene expressions

  14. Behavioral and endocrine consequences of placentophagia in male California mice (Peromyscus californicus).

    Perea-Rodriguez, Juan P; Zhao, Meng; Harris, Breanna N; Raqueno, Joel; Saltzman, Wendy

    2018-05-01

    Ingestion of placenta by mammalian mothers can lead to changes in pain sensitivity, hormone levels, and behavioral responses to newborns. In some biparental mammals, males, in addition to females, ingest placenta when their offspring are born. In the monogamous, biparental California mouse (Peromyscus californicus), males first become attracted to placenta when cohabitating with their pregnant mate, and virgin males administered placenta are less neophobic than males given oil vehicle. In this study, we investigated the effects of placentophagia on pain sensitivity, anxiety-like behavior, behavioral responses to pups, and circulating corticosterone levels of both breeding and nonbreeding male California mice. We orally administered either a conspecific placenta or oil vehicle to male mice from three reproductive conditions (first-time fathers, first-time expectant fathers, and virgin males) and tested their pain sensitivity 1 h later, as well as their exploratory behavior and paternal responsiveness in an open field 4 h post-treatment. We measured plasma corticosterone immediately after the open-field test. We found that placenta-treated males, independent of reproductive condition, traveled significantly longer distances in the open field than males treated with oil, indicative of lower anxiety. Additionally, fathers had shorter latencies to approach and to care for pups (i.e., huddling and licking pups), and spent more time engaging in these behaviors, than did age-matched expectant fathers and virgin males, independent of treatment. We found no effect on plasma corticosterone levels or pain sensitivity as a result of either treatment or reproductive condition. These findings indicate that placenta ingestion decreases anxiety-related behaviors in male California mice, but might not influence pain sensitivity, paternal responsiveness, or plasma corticosterone concentrations. Published by Elsevier Inc.

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

    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.

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

    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).

  17. Reproductive capacity of male mice protected from supralethal effect of gamma-radiation by the administration of a mixture of extracts from Archangelica officinalis and Ledus palustre

    Narimanov, A.A.

    1992-01-01

    Thirty-day old albino mongrel male mice were exposed to gamma-radiation (LD 90/30 ) after preventive single injection of a mixture of extracts from Archangelica officinalis and Ledum palustre. One month after irradiation, the survivors were mated to nonirradiated females. Healthy offspring were obtained from 11 out 12 experimental males. The number of both sexes in the posterity of nonirradiated parents was equal, whereas in offspring of experimental groups, the number of female pups was 2.3 times larger than that of males. The experimental posterity was found to be resistant to supralethal radiation doses

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

    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).

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

    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.

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

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

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

  1. Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice.

    Bouchaud, G; Castan, L; Chesné, J; Braza, F; Aubert, P; Neunlist, M; Magnan, A; Bodinier, M

    2016-01-01

    Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

    2014-07-01

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

  3. Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

    Longo, M; Jain, [No Value; Langenveld, J; Vedernikov, YP; Garfield, RE; Hankins, GDV; Anderson, GD; Saade, GR

    2004-01-01

    Objective: Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these

  4. Maternal preconceptional nutrition leads to variable fat deposition and gut dimensions of adult offspring mice (C57BL/6JBom)

    Mortensen, Elna Louise Krogh; Wang, Tobias; Malte, H.

    2010-01-01

    . There was no significant effect of maternal nutrition on dry mass of the stomach or ceca. Conclusion:   Our study shows that preconceptional nutrition can have important influence on several body features of offspring in mice, including body composition and dimensions of the digestive system....

  5. Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

    Ribes, Diana; Fuentes, Silvia; Torrente, Margarita; Colomina, M. Teresa; Domingo, Jose L.

    2010-01-01

    Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.

  6. Characterization of urinary volatiles in Swiss male mice (Mus ...

    Unknown

    Information about diet is also available in guinea pigs. (Beauchamp ... change in diet can alter urine odours. Urinary ... adult male mice, which are dependent upon high levels of ... a protein or protein related substance (Marchlewska-Koj. 1977 ...

  7. Cumulative genetic effects from exposure of male mice to tritium for ten generations

    Mewissen, D.J.; Ugarte, A.S.

    1979-01-01

    Three sublines of C57 Black/6M mice were propagated from three sibling pairs from the same litter. All breeders were weaned at 28+-2 days of age. At each generation in experimental lines weaned male breeders aged 35 days either received a single injection of tritiated thymidine (1 μCi/g of body weight) or were exposed for 5 weeks to tritiated drinking water (10 μCi/ml). At 10 weeks of age all breeders were sibling-mated. The time of delivery, the litter size and sex ratio was recorded. At each generation the offspring in the three lines were sibling-mated in the same sequence as their parents. At the 6th generation total offspring in the sibling line receiving tritiated thymidine numbered 108 versus 336 in the sibling line exposed to tritiated water, in contrast with 721 in the control sibling line. The 6th generation couples (20 in either subline) generated at the 9th generation 624 animals in the control subline versus 386 and 476 in the subline exposed to tritium. The data suggest a trend toward reduction in the subpopulation of offspring propagated from male parents exposed to tritiated water or tritiated thymidine. At the 9th generation 50 couples were assigned to a special study on reproductive fitness. The litter size was decreased and infant mortality was increased in experimental sublines (chi-square test, P<0.05). In control, as well as in experimental lines, at 70 days of age males were sibling-mated with their sisters. All animals received tap water and were not exposed at any time to tritiated thymidine or tritiated water. Preimplantation loss values were significantly increased in experimental versus control sublines (chi-square test, P<0.01). The dose to male sperm over a 35-day period was estimated at 3.7 rads from tritiated water and at 3.9 rads from tritiated thymidine under our experimental conditions

  8. The prevalence and psychosocial correlates of suicide attempts among inpatient adolescent offspring of Croatian PTSD male war veterans.

    Boričević Maršanić, Vlatka; Margetić, Branka Aukst; Zečević, Iva; Herceg, Miroslav

    2014-10-01

    Despite evidence that children of male war veterans with combat-related posttraumatic stress disorder (PTSD) are at particularly high risk for behavior problems, very little is currently known about suicidal behaviors in this population of youth. This study aimed to examine the prevalence and psychosocial correlates of suicide attempts among psychiatrically hospitalized adolescent offspring of Croatian male PTSD veterans. Participants were psychiatric inpatients, ages 12-18 years. Self-report questionnaires assessed demographics, suicide attempts, psychopathology, parenting style, and family functioning. The prevalence of suicide attempts was 61.5% (65.2% for girls and 58.0% for boys). Internalizing symptoms, family dysfunction, lower levels of maternal and paternal care, and paternal overcontrol were significantly associated with suicide attempts. Our findings suggest that suicide attempts are common among inpatient adolescent offspring of male PTSD veterans and that interventions targeting both adolescent psychopathology and family relationships are needed for adolescents who have attempted suicide.

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

    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

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

    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. Peroxisome proliferator-activated receptors-alpha and gamma are targets to treat offspring from maternal diet-induced obesity in mice.

    D'Angelo Carlo Magliano

    Full Text Available AIM: The aim of the present study was to evaluate whether activation of peroxisome proliferator-activated receptor (PPARalpha and PPARgamma by Bezafibrate (BZ could attenuate hepatic and white adipose tissue (WAT abnormalities in male offspring from diet-induced obese dams. MATERIALS AND METHODS: C57BL/6 female mice were fed a standard chow (SC; 10% lipids diet or a high-fat (HF; 49% lipids diet for 8 weeks before mating and during gestation and lactation periods. Male offspring received SC diet at weaning and were subdivided into four groups: SC, SC/BZ, HF and HF/BZ. Treatment with BZ (100 mg/Kg diet started at 12 weeks of age and was maintained for three weeks. RESULTS: The HF diet resulted in an overweight phenotype and an increase in oral glucose intolerance and fasting glucose of dams. The HF offspring showed increased body mass, higher levels of plasmatic and hepatic triglycerides, higher levels of pro-inflammatory and lower levels of anti-inflammatory adipokines, impairment of glucose metabolism, abnormal fat pad mass distribution, higher number of larger adipocytes, hepatic steatosis, higher expression of lipogenic proteins concomitant to decreased expression of PPARalpha and carnitine palmitoyltransferase I (CPT-1 in liver, and diminished expression of PPARgamma and adiponectin in WAT. Treatment with BZ ameliorated the hepatic and WAT abnormalities generated by diet-induced maternal obesity, with improvements observed in the structural, biochemical and molecular characteristics of the animals' livers and epididymal fat. CONCLUSION: Diet-induced maternal obesity lead to alterations in metabolism, hepatic lipotoxicity and adverse liver and WAT remodeling in the offspring. Targeting PPAR with Bezafibrate has beneficial effects reducing the alterations, mainly through reduction of WAT inflammatory state through PPARgamma activation and enhanced hepatic beta-oxidation due to increased PPARalpha/PPARgamma ratio in liver.

  12. Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations.

    Dai, Yun; Thamotharan, Shanthie; Garg, Meena; Shin, Bo-Chul; Devaskar, Sherin U

    2012-09-01

    Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O(2) consumption (VO(2)), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

  13. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria.

    Ankur Sharma

    Full Text Available Pregnancy malaria (PM is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6-7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis.

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

    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.

  15. Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain.

    Fang, Fangfang; Gao, Yue; Wang, Tingwei; Chen, Donglong; Liu, Jingli; Qian, Wenyi; Cheng, Jie; Gao, Rong; Wang, Jun; Xiao, Hang

    2016-03-14

    Bisphenol A (BPA), an environmental estrogenic endocrine disruptor, is widely used for producing polycarbonate plastics and epoxy resins. Available data have shown that perinatal exposure to BPA contributes to peripheral insulin resistance, while in the present study, we aimed to investigate the effects of perinatal BPA exposure on insulin signaling and glucose transport in the cortex of offspring mice. The pregnant mice were administrated either vehicle or BPA (100 μg/kg/day) at three perinatal stages. Stage I: from day 6 of gestation until parturition (P6-PND0 fetus exposure); Stage II: from lactation until delactation (PND0-PND21 newborn exposure) and Stage III: from day 6 of pregnancy until delactation (P6-PND21 fetus and newborn exposure). At 8 months of age for the offspring mice, the insulin signaling pathways and glucose transporters (GLUTs) were detected. Our data indicated that the insulin signaling including insulin, phosphorylated insulin receptor (IR), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular signal regulated protein kinase (p-ERK) were significantly decreased in the brain. In parallel, GLUTs (GLUT1/3/4) were obviously decreased as well in BPA-treated group in mice brain. Noteworthily, the phosphorylated tau (p-tau) and amyloid precursor protein (APP) were markedly up-regulated in all BPA-treated groups. These results, taken together, suggest the adverse effects of BPA on insulin signaling and GLUTs, which might subsequently contribute to the increment of p-tau and APP in the brain of adult offspring. Therefore, perinatal BPA exposure might be a risk factor for the long-term neurodegenerative changes in offspring male mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Mother's prior intrauterine position affects the sex ratio of her offspring in house mice.

    Vandenbergh, J G; Huggett, C L

    1994-11-08

    Sex ratio alterations related to environmental factors occur in several mammals, but no mechanism has been identified to explain the adjustment. Intrauterine position (IUP) may provide the context in which such alterations occur. Previous studies on house mice and gerbils reveal that the position of a fetus in the uterus in relation to the sex of its neighbors influences its later anatomy, physiology, and behavior. The anogenital distance (AGD) of females located between two males (2M) is longer than that of females not between two males (OM). We have found that the IUP, as determined by cesarean section and by an index of the AGD, correlates with the sex ratio of the litters produced by female mice. The sex ratio of the first litter born to 2M females was 58% males, for 1M females was 51% males and for OM females was 42% males. The effect on sex ratio continues into the second litter. The number of pups produced by mothers of different IUPs in her first two litters did not differ, suggesting that the sex ratio adjustment occurs prior to parturition. These results provide a basis for the natural variability observed in sex ratios of litter-bearing mammals and suggest that one or more intrauterine mechanisms may be responsible for environmentally related sex ratio alterations.

  17. Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

    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. 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

    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.

  19. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Dani Smith

    Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  20. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2015-01-01

    Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  1. Enhanced GABA action on the substantia gelatinosa neurons of the medullary dorsal horn in the offspring of streptozotocin-injected mice.

    Nguyen, Hoang Thi Thanh; Bhattarai, Janardhan Prasad; Park, Soo Joung; Lee, Jeong Chae; Cho, Dong Hyu; Han, Seong Kyu

    2015-07-01

    Peripheral neuropathy is a frequent complication of diabetes mellitus and a common symptom of neuropathic pain, the mechanism of which is complex and involves both peripheral and central components of the sensory system. The lamina II of the medullary dorsal horn, called the substantia gelatinosa (SG), is well known to be a critical site for processing of orofacial nociceptive information. Although there have been a number of studies done on diabetic neuropathy related to the orofacial region, the action of neurotransmitter receptors on SG neurons in the diabetic state is not yet fully understood. Therefore, we used the whole-cell patch clamp technique to investigate this alteration on SG neurons in both streptozotocin (STZ)-induced diabetic mice and offspring from diabetic female mice. STZ (200 mg/kg)-injected mice showed a small decrease in body weight and a significant increase in blood glucose level when compared with their respective control group. However, application of different concentrations of glycine, gamma-aminobutyric acid (GABA) and glutamate on SG neurons from STZ-injected mice did not induce any significant differences in inward currents when compared to their control counterparts. On the other hand, the offspring of diabetic female mice (induced by multiple injections of STZ (40 mg/kg) for 5 consecutive days) led to a significant decrease in both body weight and blood glucose level compared to the control offspring. Glycine and glutamate responses in the SG neurons of the offspring from diabetic female mice were similar to those of control offspring. However, the GABA response in SG neurons of offspring from diabetic female mice was greater than that of control offspring. Furthermore, the GABA-mediated responses in offspring from diabetic and control mice were examined at different concentrations ranging from 3 to 1,000 μM. At each concentration, the GABA-induced mean inward currents in the SG neurons of offspring from diabetic female mice were

  2. Mother's prior intrauterine position affects the sex ratio of her offspring in house mice.

    Vandenbergh, J G; Huggett, C L

    1994-01-01

    Sex ratio alterations related to environmental factors occur in several mammals, but no mechanism has been identified to explain the adjustment. Intrauterine position (IUP) may provide the context in which such alterations occur. Previous studies on house mice and gerbils reveal that the position of a fetus in the uterus in relation to the sex of its neighbors influences its later anatomy, physiology, and behavior. The anogenital distance (AGD) of females located between two males (2M) is lon...

  3. Effects of the use of assisted reproductive technologies and an obesogenic environment on resistance artery function and diabetes biomarkers in mice offspring.

    Francisco I Ramirez-Perez

    Full Text Available Maternal obesity affects the incidence of cardiovascular disease and diabetes in offspring. Also the use of assisted reproductive technologies (ART has been associated with cardiovascular deficiencies in offspring. Obese women often suffer from infertility and use ART to achieve a pregnancy, but the combined effects of maternal obesity and ART on cardiovascular health and incidence of diabetes in the offspring is not known. Here, we report the effects of the use of ART within an obesogenic environment, consisting of feeding a western diet (WD to dams and offspring, on resistance artery function and presence of diabetes biomarkers in juvenile mice offspring. Our results indicate that WD and ART interacted to induce endothelial dysfunction in mesenteric resistance arteries isolated from 7-week-old mice offspring. This was determined by presence of a reduced acetylcholine-induced dilation compared to controls. The arteries from these WD-ART mice also had greater wall cross-sectional areas and wall to lumen ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers measured, only resistin was affected by a WD×ART interaction. Serum resistin was significantly greater in WD-ART offspring compared to controls. Diet and sex effects were observed in other diabetes biomarkers. Our conclusion is that in mice the use of ART within an obesogenic environment interacts to favor the development of endothelial dysfunction in the resistance arteries of juvenile offspring, while having marginal effects on diabetes biomarkers.

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

    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.

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

    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

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

    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.

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

    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.)

  8. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

    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.

  9. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

    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.

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

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

    2008-01-01

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

  11. Cardamom (Elettaria cardamomum perinatal exposure effects on the development, behavior and biochemical parameters in mice offspring

    Gasem Mohammad Abu-Taweel

    2018-01-01

    Full Text Available Cardamom is a strong antioxidant plant, so it is called the queen of spices. In the present study, we explored the potentials of cardamom on developmental, learning ability and biochemical parameters of mice offspring. Thirty pregnant mice were allocated to three groups of ten animals in each. Groups Π and Ш received pilsbury's Diet containing 10 and 20% of cardamom (w/w respectively, whereas Group I used as control. Cardomom was administered from the first day of pregnancy and was continued until post-natal day 15 (PD 15 and thereafter the mothers were switched to plain pilsbury's Diet. During the weaning period, three pups in each litter were color marked from the others, and were subjected to various tests (Physical assessment such body weight and eye opening and hair appearance; the neuromaturation of reflexes like righting, rotating, and cliff avoidance reflexes; learning ability and memory retention; estimation of monoamines neurotransmitters like dopamine and serotonin, non-enzymatic oxidative stress such as TBARS and GSH in forebrain at different ages of pups. The results indicated that the body weight gain was declining significantly. Hair appearance and eyes opening were delayed significantly. Righting, rotating, and cliff avoidance reflexes were delayed in treated animals. Exposure to cardamom led to enhance learning and memory retention as compared to control. Monoamines (DA, 5-HT and GSH were elevated, whereas TBARS was inhibited significantly. In conclusion, perinatal cardamom exposure enhanced learning and memory as compared to control. Cardamom and its benefit compounds were transported via placenta or/and milk during lactation. Cardamom needs more researches to investigate its benefits on other kinds of behavior.

  12. Cardamom (Elettaria cardamomum) perinatal exposure effects on the development, behavior and biochemical parameters in mice offspring.

    Abu-Taweel, Gasem Mohammad

    2018-01-01

    Cardamom is a strong antioxidant plant, so it is called the queen of spices. In the present study, we explored the potentials of cardamom on developmental, learning ability and biochemical parameters of mice offspring. Thirty pregnant mice were allocated to three groups of ten animals in each. Groups Π and Ш received pilsbury's Diet containing 10 and 20% of cardamom (w/w) respectively, whereas Group I used as control. Cardomom was administered from the first day of pregnancy and was continued until post-natal day 15 (PD 15) and thereafter the mothers were switched to plain pilsbury's Diet. During the weaning period, three pups in each litter were color marked from the others, and were subjected to various tests (Physical assessment such body weight and eye opening and hair appearance; the neuromaturation of reflexes like righting, rotating, and cliff avoidance reflexes; learning ability and memory retention; estimation of monoamines neurotransmitters like dopamine and serotonin, non-enzymatic oxidative stress such as TBARS and GSH in forebrain at different ages of pups). The results indicated that the body weight gain was declining significantly. Hair appearance and eyes opening were delayed significantly. Righting, rotating, and cliff avoidance reflexes were delayed in treated animals. Exposure to cardamom led to enhance learning and memory retention as compared to control. Monoamines (DA, 5-HT) and GSH were elevated, whereas TBARS was inhibited significantly. In conclusion, perinatal cardamom exposure enhanced learning and memory as compared to control. Cardamom and its benefit compounds were transported via placenta or/and milk during lactation. Cardamom needs more researches to investigate its benefits on other kinds of behavior.

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

    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.

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

    Clint Gray

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

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

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

    2010-01-01

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

  16. [The reproductive correlates of social hierarchy in laboratory male mice].

    Osadchuk, L B; Salomacheva, I N; Bragin, A V; Osadchuk, A V

    2007-01-01

    In laboratory male mice the effects of social hierarchy on hormonal and spermatogenic testicular function, accessory organs and testicular weights, sexual behaviour have been investigated using an experimental model of social hierarchy, which is characterised by a minimal size (two male mice) and 5 days period of social interactions. The social rank of the partners was detected by asymmetry in aggressive behaviour. Using the experimental condition, when the both partners have no preferences for exclusive use of area we demonstrated that there were no rank differences in the number of mounts and testicular testosterone content. Nevertheless a rank asymmetry in the male sniffing behaviour towards a receptive female, weights of the testes, seminal vesicles, epididymes and the number of epididymal sperm was kept up in a stable social group. Social dominance was found to affect negatively on testicular testosterone increase in response to introduction of a receptive female and sexual attractiveness of male to a receptive female in both dominant and subordinate males. The results obtained demonstrate the impact of social hierarchy on reproduction in laboratory male mice, particular in respect of spermatogenesis and the testicular testosterone in response to a receptive female.

  17. Taurine and β-alanine intraperitoneal injection in lactating mice modifies the growth and behavior of offspring.

    Nishigawa, Takuma; Nagamachi, Satsuki; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

    2018-01-08

    Taurine, one of the sulfur-containing amino acids, has several functions in vivo. It has been reported that taurine acts on γ-aminobutyric acid receptors as an agonist and to promote inhibitory neurotransmission. Milk, especially colostrum, contains taurine and it is known that milk taurine is essential for the normal development of offspring. β-Alanine is transported via a taurine transporter and a protein-assisted amino acid transporter, the same ones that transport taurine. The present study aimed to investigate whether the growth and behavior of offspring could be altered by modification of the taurine concentration in milk. Pregnant ICR mice were separated into 3 groups: 1) a control group, 2) a taurine group, and 3) a β-alanine group. During the lactation periods, dams were administered, respectively, with 0.9% saline (10 ml/kg, i.p.), taurine dissolved in 0.9% saline (43 mg/10 ml/kg, i.p.), or β-alanine dissolved in 0.9% saline (31 mg/10 ml/kg, i.p.). Interestingly, the taurine concentration in milk was significantly decreased by the administration of β-alanine, but not altered by the taurine treatment. The body weight of offspring was significantly lower in the β-alanine group. β-Alanine treatment caused a significant decline in taurine concentration in the brains of offspring, and it was negatively correlated with total distance traveled in the open field test at postnatal day 15. Thus, decreased taurine concentration in the brain induced hyperactivity in offspring. These results suggested that milk taurine may have important role of regulating the growth and behavior of offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    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...

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

    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.

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

    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. 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.

    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.

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

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

    2018-02-01

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

  3. Epigenomic profiling in visceral white adipose tissue of offspring of mice exposed to late gestational sleep fragmentation.

    Cortese, R; Khalyfa, A; Bao, R; Andrade, J; Gozal, D

    2015-07-01

    Sleep fragmentation during late gestation (LG-SF) is one of the major perturbations associated with sleep apnea and other sleep disorders during pregnancy. We have previously shown that LG-SF induces metabolic dysfunction in offspring mice during adulthood. To investigate the effects of late LG-SF on metabolic homeostasis in offspring and to determine the effects of LG-SF on the epigenome of visceral white adipose tissue (VWAT) in the offspring. Time-pregnant mice were exposed to LG-SF or sleep control during LG (LG-SC) conditions during the last 6 days of gestation. At 24 weeks of age, lipid profiles and metabolic parameters were assessed in the offspring. We performed large-scale DNA methylation analyses using methylated DNA immunoprecipitation (MeDIP) coupled with microarrays (MeDIP-chip) in VWAT of 24-week-old LG-SF and LG-SC offspring (n=8 mice per group). Univariate multiple-testing adjusted statistical analyses were applied to identify differentially methylated regions (DMRs) between the groups. DMRs were mapped to their corresponding genes, and tested for potential overlaps with biological pathways and gene networks. We detected significant increases in body weight (31.7 vs 28.8 g; P=0.001), visceral (642.1 vs 497.0 mg; P=0.002) and subcutaneous (293.1 vs 250.1 mg; P=0.001) fat mass, plasma cholesterol (110.6 vs 87.6 mg dl(-1); P=0.001), triglycerides (87.3 vs 84.1 mg dl(-1); P=0.003) and homeostatic model assessment-insulin resistance values (8.1 vs 6.1; P=0.007) in the LG-SF group. MeDIP analyses revealed that 2148 DMRs (LG-SF vs LG-SC; Pgenes have reported functions that are altered in obesity and metabolic syndrome, such as Cartpt, Akt2, Apoe, Insr1 and so on. Overrepresented pathways and gene networks were related to metabolic regulation and inflammatory response. Our findings show a major role for epigenomic regulation of pathways associated with the metabolic processes and inflammatory responses in VWAT. LG-SF-induced epigenetic

  4. Maternal Diet-Induced Obesity Programmes Cardiac Dysfunction in Male Mice Independently of Post-Weaning Diet.

    Loche, Elena; Blackmore, Heather L; Carpenter, Asha A M; Beeson, Jessica H; Pinnock, Adele; Ashmore, Thomas J; Aiken, Catherine E; de Almeida-Faria, Juliana; Schoonejans, Josca; Giussani, Dino A; Fernandez-Twinn, Denise S; Ozanne, Susan E

    2018-04-04

    Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity. The impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure and function was assessed in 8-week old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P<0.0001) and leptin levels (P<0.0001); maternal obesity (P=0.001) and a post-weaning obesogenic diet (P=0.002) increased absolute heart weight; maternal obesity (P=0.01) and offspring obesity (P=0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7:Myh6 ratio; P=0.0004), however these genes were not affected by offspring diet; maternal obesity (P=0.02) and offspring obesity (P=0.05) caused hypertension and effects were additive. Maternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes and remodelling of cardiac structure. These data highlight that the

  5. Cross-generational impact of a male murine pheromone 2-sec-butyl-4,5-dihydrothiazole in female mice

    Koyama, Sachiko; Soini, Helena A.; Wager-Miller, James; Alley, William R.; Pizzo, Matthew J.; Rodda, Cathleen; Alberts, Jeffrey; Crystal, Jonathon D.; Lai, Cary; Foley, John; Novotny, Milos V.

    2015-01-01

    The current understanding of the activity of mammalian pheromones is that endocrine and behavioural effects are limited to the exposed individuals. Here, we demonstrate that the nasal exposure of female mice to a male murine pheromone stimulates expansion of mammary glands, leading to prolonged nursing of pups. Subsequent behavioural testing of the pups from pheromone-exposed dams exhibited enhanced learning. Sialic acid components in the milk are known to be involved in brain development. We hypothesized that the offspring might have received more of this key nutrient that promotes brain development. The mRNA for polysialyltransferase, which produces polysialylated neural cell adhesion molecules related to brain development, was increased in the brain of offspring of pheromone-exposed dams at post-natal day 10, while it was not different at embryonic stages, indicating possible differential brain development during early post-natal life. PMID:26136453

  6. Intergenerational Influence of Paternal Obesity on Metabolic and Reproductive Health Parameters of the Offspring: Male-Preferential Impact and Involvement of Kiss1-Mediated Pathways.

    Sanchez-Garrido, Miguel Angel; Ruiz-Pino, Francisco; Velasco, Inmaculada; Barroso, Alexia; Fernandois, Daniela; Heras, Violeta; Manfredi-Lozano, Maria; Vazquez, Maria Jesus; Castellano, Juan Manuel; Roa, Juan; Pinilla, Leonor; Tena-Sempere, Manuel

    2018-02-01

    Obesity and its comorbidities are reaching epidemic proportions worldwide. Maternal obesity is known to predispose the offspring to metabolic disorders, independently of genetic inheritance. This intergenerational transmission has also been suggested for paternal obesity, with a potential negative impact on the metabolic and, eventually, reproductive health of the offspring, likely via epigenetic changes in spermatozoa. However, the neuroendocrine component of such phenomenon and whether paternal obesity sensitizes the offspring to the disturbances induced by high-fat diet (HFD) remain poorly defined. We report in this work the metabolic and reproductive impact of HFD in the offspring from obese fathers, with attention to potential sex differences and alterations of hypothalamic Kiss1 system. Lean and obese male rats were mated with lean virgin female rats; male and female offspring were fed HFD from weaning onward and analyzed at adulthood. The increases in body weight and leptin levels, but not glucose intolerance, induced by HFD were significantly augmented in the male, but not female, offspring from obese fathers. Paternal obesity caused a decrease in luteinizing hormone (LH) levels and exacerbated the drop in circulating testosterone and gene expression of its key biosynthetic enzymes caused by HFD in the male offspring. LH responses to central kisspeptin-10 administration were also suppressed in HFD males from obese fathers. In contrast, paternal obesity did not significantly alter gonadotropin levels in the female offspring fed HFD, although these females displayed reduced LH responses to kisspeptin-10. Our findings suggest that HFD-induced metabolic and reproductive disturbances are exacerbated by paternal obesity preferentially in males, whereas kisspeptin effects are affected in both sexes. Copyright © 2018 Endocrine Society.

  7. Comparison of growth-related traits and gene expression profiles between the offspring of neomale (XX) and normal male (XY) rainbow trout.

    Kocmarek, Andrea L; Ferguson, Moira M; Danzmann, Roy G

    2015-04-01

    All-female lines of fish are created by crossing sex reversed (XX genotype) males with normal females. All-female lines avoid the deleterious phenotypic effects that are typical of precocious maturation in males. To determine whether all-female and mixed sex populations of rainbow trout (Oncorhynchus mykiss) differ in performance, we compared the growth and gene expression profiles in progeny groups produced by crossing a XX male and a XY male to the same five females. Body weight and length were measured in the resulting all-female (XX) and mixed sex (XX/XY) offspring groups. Microarray experiments with liver and white muscle were used to determine if the gene expression profiles of large and small XX offspring differ from those in large and small XX/XY offspring. We detected no significant differences in body length and weight between offspring groups but XX offspring were significantly less variable in the value of these traits. A large number of upregulated genes were shared between the large XX and large XX/XY offspring; the small XX and small XX/XY offspring also shared similar expression profiles. No GO category differences were seen in the liver or between the large XX and large XX/XY offspring in the muscle. The greatest differences between the small XX and small XX/XY offspring were in the genes assigned to the "small molecule metabolic process" and "cellular metabolic process" GO level 3 categories. Similarly, genes within these categories as well as the category "macromolecule metabolic process" were more highly expressed in small compared to large XX fish.

  8. Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring

    Yao-hua KE; Chun WANG; Yun-qiu HU; Miao LI; Yu-juan LIU; Wen-zhen FU; Zhen-lin ZHANG; Wen-jin XIAO; Jin-wei HE; Hao ZHANG; Jin-bo YU; Wei-wei HU; Jie-mei GU; Gao GAO; Hua YUE

    2012-01-01

    Aim:Genetic variation in ALOX12,which encoded human 12-lipoxygenase,was found to be associated with fat mass in young Chinese men.The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese nuclear families with male offspring.Methods:We recruited 1,296 subjects from 427 nuclear families with male offspring and genotyped five SNPs (rs9894225,rs748694,rs2619112,rs2619118,and rs916055) in the ALOX15 gene locus.The total fat mass (TFM),trunk fat mass (tFM),leg fat mass (LFM) and arm fat mass (AFM) were measured using dual-energy X-ray absorptiometry (DXA).The percentage of fat mass (PFM) was the ratio of TFM and body weight.The association between SNPs and haplotypes of ALOX15 and obesity-related phenotypic variation was measured using quantitative transmission disequilibrium test (QTDT).Results:Using QTDT to measure family-based genetic association,we found that rs916055 had a statistically significant association with PFM (P=0.038),whereas rs916055 had a marginal but statistically insignificant association with tFM (P=0.093).The multipleparameter 1000 permutations test agreed with the family-based association results:both showed that rs916055 had a statistically significant association with PFM (P=0.033).Conclusion:rs916055 in ALOX15 gene was significantly associated with the percentage of fat mass in Chinese nuclear families with male offspring in the family-based association study using QTDT approach.

  9. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

    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.

  10. Histomorphological effects of isoniazid induced hepatotoxicity in male albino mice

    Humayun, F.; Zareen, N.

    2017-01-01

    To observe the histomorphological changes of isoniazid induced hepatotoxicity in male albino mice. Methodology: This experimental study was carried out at University of Health Sciences, Lahore, Pakistan from January to December 2013. Forty male albino mice selected by simple random technique, were divided into two groups; A-Control, and B-experimental. Group A comprised of 15, while Group B comprised 25 mice. Both the groups were kept under identical conditions and diet. However, experimental group was treated with an additional oral hepatotoxic dose of isoniazid i.e. 100mg/kg bodyweight daily for 30 days. After 30 days, the animals were sacrificed and livers were dissected out. Gross comparison of the organ and stained sections were histologically compared for morphological differences between the groups. Fischer Exact test was used to analyze the qualitative data and a p<0.05 was considered significant. Results: Group A animals showed the normal liver architecture. Whereas, those of Group B showed deranged hepatic histomorphology. Conclusion: Hepatotoxic dose of Isoniazid caused histomorphological alterations in the liver of male albino mice. (author)

  11. Genetics and evolution of hybrid male sterility in house mice.

    White, Michael A; Stubbings, Maria; Dumont, Beth L; Payseur, Bret A

    2012-07-01

    Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F(2) intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F(2) intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.

  12. Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

    Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

    2017-10-15

    Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy

    Rebecca Oelkrug; Beate Herrmann; Cathleen Geissler; Lisbeth Harder; Christiane Koch; Hendrik Lehnert; Henrik Oster; Henriette Kirchner; Jens Mittag

    2017-01-01

    Objective: Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is know...

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

    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.

  15. A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice.

    Eunice H Chin

    Full Text Available Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.

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

    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

  17. NMDA receptor activation upstream of methyl farnesoate signaling for short day-induced male offspring production in the water flea, Daphnia pulex.

    Toyota, Kenji; Miyakawa, Hitoshi; Yamaguchi, Katsushi; Shigenobu, Shuji; Ogino, Yukiko; Tatarazako, Norihisa; Miyagawa, Shinichi; Iguchi, Taisen

    2015-03-14

    The cladoceran crustacean Daphnia pulex produces female offspring by parthenogenesis under favorable conditions, but in response to various unfavorable external stimuli, it produces male offspring (environmental sex determination: ESD). We recently established an innovative system for ESD studies using D. pulex WTN6 strain, in which the sex of the offspring can be controlled simply by changes in the photoperiod: the long-day and short-day conditions can induce female and male offspring, respectively. Taking advantage of this system, we demonstrated that de novo methyl farnesoate (MF) synthesis is necessary for male offspring production. These results indicate the key role of innate MF signaling as a conductor between external environmental stimuli and the endogenous male developmental pathway. Despite these findings, the molecular mechanisms underlying up- and downstream signaling of MF have not yet been well elucidated in D. pulex. To elucidate up- and downstream events of MF signaling during sex determination processes, we compared the transcriptomes of daphnids reared under the long-day (female) condition with short-day (male) and MF-treated (male) conditions. We found that genes involved in ionotropic glutamate receptors, known to mediate the vast majority of excitatory neurotransmitting processes in various organisms, were significantly activated in daphnids by the short-day condition but not by MF treatment. Administration of specific agonists and antagonists, especially for the N-methyl-D-aspartic acid (NMDA) receptor, strongly increased or decreased, respectively, the proportion of male-producing mothers. Moreover, we also identified genes responsible for male production (e.g., protein kinase C pathway-related genes). Such genes were generally shared between the short-day reared and MF-treated daphnids. We identified several candidate genes regulating ESD which strongly suggests that these genes may be essential factors for male offspring production as an

  18. Hypogonadism alters cecal and fecal microbiota in male mice.

    Harada, Naoki; Hanaoka, Ryo; Hanada, Kazuki; Izawa, Takeshi; Inui, Hiroshi; Yamaji, Ryoichi

    2016-11-01

    Low testosterone levels increase the risk for cardiovascular disease in men and lead to shorter life spans. Our recent study showed that androgen deprivation via castration altered fecal microbiota and exacerbated risk factors for cardiovascular disease, including obesity, impaired fasting glucose, excess hepatic triglyceride accumulation, and thigh muscle weight loss only in high-fat diet (HFD)-fed male mice. However, when mice were administered antibiotics that disrupted the gut microbiota, castration did not increase cardiovascular risks or decrease the ratio of dried feces to food intake. Here, we show that changes in cecal microbiota (e.g., an increased Firmicutes/Bacteroidetes ratio and number of Lactobacillus species) were consistent with changes in feces and that there was a decreased cecal content secondary to castration in HFD mice. Castration increased rectal body temperature and plasma adiponectin, irrespective of diet. Changes in the gut microbiome may provide novel insight into hypogonadism-induced cardiovascular diseases.

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

    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.

  20. Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

    Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

    2016-01-01

    The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

  1. Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring.

    Andretta, Rhayza Roberta; Okada, Fatima Kazue; Paccola, Camila Cicconi; Stumpp, Taiza; de Oliva, Samara Urban; Miraglia, Sandra M

    2014-04-01

    Carbamazepine (CBZ) is an anti-epileptic drug that acts on Leydig cells, affecting steroidogenesis and causes fetal malformation. The aim of this study was to investigate the effects of CBZ on male sexual maturation and other male parameters. Rat dams were treated with CBZ during pregnancy and breastfeeding. The anogenital distance (AGD) and the anogenital index (AGI) were obtained. Testicular descent and preputial separation were also evaluated. The offspring was euthanized at PND 41 and 63. The accessory glands were weighed and the testes were collected for histopathological, morphometric and sterological analyses. The numerical density of Leydig cells and hormone dosage were obtained. CBZ caused an increase of AGI and a delay of testicular descent and of preputial separation. CBZ also caused a decrease of testosterone level and of sperm count and an increase of abnormal sperm. These results indicate that CBZ delays puberty onset and affects steroidogenesis and sperm quality. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Preliminary study on influences of radioactivity of residential granite building materials upon parent mice and their offspring

    Liang Minyi; Zhang Jinghong; Zhu Weiyun; Li Yinyan; Liang Yongqing; Zhang Songshuan; Zhu Daming; Li Jinlin; Lu Qingpu

    2006-01-01

    Objective: To observe the effects of radioactivity of the residential granite building materials on the survival and fertility of mice. Methods: The radioactivities of A, B, C, and D granite building materials were measured and screened by gamma-ray spectrometer, and then these materials were placed into the mice cages. The residential radon was measured with solid state nuclear track detector's and 24-hour continuous measurement. Ninety-six healthy and ablactated mice were randomly selected and put into the four animal cages with different levels of radioactivity, and fed for 120 days. Mice mated and bred naturally. The fertilities and survivals of P, F 1 , and F 2 generation were observed and analyzed. Results: External exposures in the four mice cages were higher than those from the internal exposure. The differences of rates of pregnancy, abortion, and infertility between the P and F 1 generations had no statistical significance among all the groups after being fed for 120 days (P>0.05). There was significant difference among each group in the fertility of F 1 generation (P< 0.001), and the survival rates of the offspring were decreased with increase of radioactivity in granite building materials (P<0.001). Conclusion: Compared with the residential radon, the gamma rays released from the granite building materials had a greater influence on animals. The study suggested that different granite building materials had different influences on the survival and fertility of mice. (authors)

  3. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Impairment of fear memory consolidation in maternally stressed male mouse offspring: evidence for nongenomic glucocorticoid action on the amygdala.

    Lee, Eun Jeong; Son, Gi Hoon; Chung, Sooyoung; Lee, Sukwon; Kim, Jeongyeon; Choi, Sukwoo; Kim, Kyungjin

    2011-05-11

    The environment in early life elicits profound effects on fetal brain development that can extend into adulthood. However, the long-lasting impact of maternal stress on emotional learning remains largely unknown. Here, we focus on amygdala-related learning processes in maternally stressed mice. In these mice, fear memory consolidation and certain related signaling cascades were significantly impaired, though innate fear, fear memory acquisition, and synaptic NMDA receptor expression in the amygdala were unaltered. In accordance with these findings, maintenance of long-term potentiation (LTP) at amygdala synapses, but not its induction, was significantly impaired in the maternally stressed animals. Interestingly, amygdala glucocorticoid receptor expression was reduced in the maternally stressed mice, and administration of glucocorticoids (GCs) immediately after fear conditioning and LTP induction restored memory consolidation and LTP maintenance, respectively, suggesting that a weakening of GC signaling was responsible for the observed impairment. Furthermore, microinfusion of a membrane-impermeable form of GC (BSA-conjugated GC) into the amygdala mimicked the restorative effects of GC, indicating that a nongenomic activity of GC mediates the restorative effect. Together, these findings suggest that prenatal stress induces long-term dysregulation of nongenomic GC action in the amygdala of adult offspring, resulting in the impairment of fear memory consolidation. Since modulation of amygdala activity is known to alter the consolidation of emotionally influenced memories allocated in other brain regions, the nongenomic action of GC on the amygdala shown herein may also participate in the amygdala-dependent modulation of memory consolidation.

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

    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

  6. Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

    Dalterio, S; Steger, R; Mayfield, D; Bartke, A

    1984-01-01

    Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

  7. Male rock sparrows differentially allocate nest defence but not food provisioning to offspring

    Matessi, Giuliano; Carmagnani, Cristina; Griggio, Matteo

    2009-01-01

    for a number of species, while male differential allocation based on female secondary sexual traits has received less attention. Yet females of many species, among birds in particular, are ornamented. We performed a test of male differential allocation based on a female ornament in the rock sparrow (Petronia...... allocation and are in agreement with previous tests of male differential allocation in rock sparrows....

  8. Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice.

    Anke Wittmann

    Full Text Available Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.

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

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

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

    2015-08-01

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

  11. Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive toxicity in testis on male offspring.

    Zhang, Ling; Zhang, Hui; Zhang, Huan; Benson, Mikael; Han, Xiaodong; Li, Dongmei

    2017-07-01

    In the present study, we evaluated the toxic effects on the testis of the male offspring of MC-LR exposure during fetal and lactational periods. Pregnant females were distributed into two experimental groups: control group and MC-LR group which were exposed to 0 and 10 μg/L of MC-LR, respectively, through drinking water separately during fetal and lactational periods. At the age of 30 days after birth, the male offspring were euthanized. The body weight, testis index, and histomorphology change were observed and the global changes of piwi-interacting RNA (piRNA) expression were evaluated. The results revealed that MC-LR was found in the testis of male offspring, body weight and testis index decreased significantly, and testicular tissue structure was damaged in the MC-LR group. In addition, the exposure to MC-LR resulted in an altered piRNA expression profile and an increase of the cell apoptosis and a decrease of the cell proliferation in the testis of the male offspring. It was reasonable to speculate that the toxic effects on reproductive system of the male offspring in MC-LR group might be mediated by piRNAs through the regulation of the target genes. As far as we are aware, this is the first report showing that MC-LR could play a role in disorder of proliferative and cell apoptosis in the testis of the male offspring by the maternal transmission effect of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice.

    Masuyama, Hisashi; Hiramatsu, Yuji

    2012-07-15

    The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

  13. Effects of 2450 MHz microwave radiation on meiosis and reproduction in male mice

    Manikowska-Czerska, E.; Czerski, P.; Leach, W.M.

    1988-01-01

    A series of studies to examine effects od continuous wave 2450 MHz radiation on meiosis and on chromosomes of germ cells in male CBA/CAY or ICR mice, by means of the spermatocyte (SCT), heritable translocation (HTT) and dominant lethal (DLT) tests is presented. Animals were exposed in an environmentally controlled waveguide system during two consecutive weeks, 30 minutes daily, six days a week. Specific absorption rates (SAR) were used in the range from 0.05 to 20 W/kg. With the SCT, it was demonstrated that chromosomal translocations can be induced by exposure during the first meiotic prophase, particularly during initial and early pachytene stages. The HTT results demonstrated that balanced translocations may be recovered among offspring of exposed males. The DLT provided confirmatory data on effects during prophase and indicated that chromosomal damage may be also induced by exposure of spermatids, during the maturation stage, and of spermatozoa. No changes were observed in spermatogonia. Thus, the effects of exposure were limited to one spermatogenic cycle. Genetically significant effects were induced at an SAR of 2 W/kg in the testes. For comparison, an SAR of 0.4 W/kg is used commonly as a basis for occupational exposure limits

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

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

    2013-01-01

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

  15. Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

    Workman, Joanna L; Weber, Michael D; Nelson, Randy J

    2011-09-30

    Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

    Rowe, Alexander M.; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B.

    2006-01-01

    Atrazine is a widely used herbicide applied to corn, sugar and other crops as a broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that prenatal/lactational exposure to atrazine alters adult immune function. Pregnant Balb/c dams were exposed subcutaneously for 21 days via time release pellets to 700 μg per day of atrazine beginning between days 10 and 12 of pregnancy. Prenatal/Lactational exposure caused no overt physical malformations in the offspring and had no effect on the number of litters carried to term or the litter size. Upon reaching early adulthood (approximately 3 months of age), the state of their immune system was evaluated. There were no changes in body weight or in the organ to body weight ratio of the spleen. Additionally, no changes were observed in the number of CD8 + T cell, CD4 + T cell, or B220 + B cell subpopulations in the spleen. T cell function was assessed by measuring proliferation and cytolytic activity after in vitro allogeneic stimulation. Male mice which had been prenatally/lactationally exposed to atrazine had an increase in both T cell proliferation and cytolytic activity. The humoral immune response was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP). There was a significant increase in the number of HKSP-specific IgM secreting B cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as atrazine is a widespread environmental contaminant, this immunopotentiation raises concerns that it may potentiate clinical diseases, such as autoimmune disease and hypersensitivity, and needs to be carefully monitored and studied

  17. Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring's liver and skeletal muscle; protective effect of taurine

    Mortensen, Ole Hartvig; Olsen, Hanne Lodberg; Frandsen, Lis

    2010-01-01

    We examined gene expression changes in liver and skeletal muscle of newborn mice subjected to a maternal low protein (LP) or normal protein (NP) diet during pregnancy, with or without taurine supplementation in the drinking water. LP offspring had a 40% lower birthweight than NP offspring, whereas...... it was reduced by only 20% with taurine supplementation. Microarray gene expression analysis revealed significant changes in 2012 genes in liver and 967 genes in skeletal muscle of LP offspring. By unknown mechanisms, taurine partially or fully prevented 30 and 46% of these expression changes, respectively....... Mitochondrial genes, in particular genes associated with oxidative phosphorylation, were more abundantly changed in LP offspring, with primarily up-regulation in liver but down-regulation in skeletal muscle. In both tissues, citrate synthase activity remained unchanged. Taurine preferentially rescued changes...

  18. Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning.

    Shomonov-Wagner, Limor; Raz, Amiram; Leikin-Frenkel, Alicia

    2015-02-26

    Alpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning. 3 month old C57Bl6/J female mice were fed diets containing normal amount of calories but rich in SFA alone or partially replaced with ALA, DHA or EPA before mating, during pregnancy and lactation. Pregnant mice fed SFA produced offspring with the highest HOMA index, liver lipids and desaturase activities. ALA prevented SFA induced lipid increase but DHA and EPA only reduced it by 42% and 31% respectively. ALA, DHA and EPA decreased HOMA index by 84%, 75% and 83% respectively. ALA, DHA and EPA decreased Δ6 and SCD1 desaturase activities about 30%. SFA feeding to mothers predisposes their offspring to develop IR and liver lipid accumulation already at weaning. ω3 fatty acids reduce IR, ALA halts lipid accumulation whereas DHA and EPA only blunt it.ALA and DHA restore the increased SCD1 to normal. These studies suggest that ω-3 fatty acids have different potencies to preclude lipid accumulation in the offspring partially by affecting pathways associated to SCD1 modulation.

  19. Wild-Type Male Offspring of fmr-1+/− Mothers Exhibit Characteristics of the Fragile X Phenotype

    Zupan, Bojana; Toth, Miklos

    2008-01-01

    Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast ...

  20. Pollen gene flow, male reproductive success, and genetic correlations among offspring in a northern red oak (Quercus rubra L.) seed orchard

    Woeste, Keith

    2017-01-01

    Northern red oak is a high-value hardwood used for lumber, furniture and veneer. Intensively managed northern red oak seed orchards are required to obtain genetic gain for trait improvement. Data from conifer seed orchards and natural and managed stands of hardwood trees have shed light on the distance over which pollen can move, and underscore the need for managerial attention to seed orchard design, placement, and maintenance. We used eleven microsatellite markers to investigate pollen gene flow, female mate choice, and male reproductive success in a clonal seed orchard of northern red oak based on paternity analysis of seed orchard offspring in progeny tests. Nearly all (93%) offspring were sired by a male parent within the seed orchard. The mean number of male parents per year was 69.5, or 47.6% of all clones in the seed orchard. Female clones in the early phenology group had more offspring sired from extra-orchard pollen (13%) than clones in the intermediate (5%) and late (1%) phenology groups. Distance was the largest influence on pollination success, and pollination occurred most often by male trees in the same subline as the maternal tree. Males in the early phenology group sired more offspring overall in the progeny pool and more offspring per mother tree than males in the intermediate or late phenology groups. Average genetic correlations among all OP progeny ranged between 0.2557 and 0.3529 with a mean of 0.28±0.01. The importance of progeny test genotyping for northern red oak improvement likely is increasing with the demand for improved varieties. The current study demonstrated the feasibility of post hoc assembly of full-sib families for genetic analysis. PMID:28166543

  1. Effect of inulin supplementation in male mice fed with high fat diet on ...

    Purpose: To evaluate the preventive and therapeutic effects of inulin supplementation in Naval Medical Research Institute (NMRI) male mice fed with high fat diet. Methods: NMRI male mice (n = 36) were divided into three groups. Control (C1), obese (O1) and experimental mice (E1) were fed during 8 weeks as follows: C1 ...

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

    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.

  3. Self-Reported Emotional and Behavioral Problems, Family Functioning and Parental Bonding among Psychiatric Outpatient Adolescent Offspring of Croatian Male Veterans with Partial PTSD

    Sarajlic Vukovic, Iris; Boricevic Maršanic, Vlatka; Aukst Margetic, Branka; Paradžik, Ljubica; Vidovic, Domagoj; Buljan Flander, Gordana

    2015-01-01

    Background: Posttraumatic stress disorder (PTSD) in male veterans has been linked with impaired family relationships and psychopathology in their children. Less is known about symptoms in children of veterans with partial PTSD. Objective: To compare mental health problems, family functioning and parent-child bonding among adolescent offspring of…

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

    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.

  5. Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice.

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2016-10-01

    Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha (Gadd45a), aryl hydrocarbon receptor (Ahr), and cyclin-dependent kinase inhibitor 1A (P21) was seen in CSC exposed testes. Apoptotic germ cell death was detected by induction of Fas, FasL, and activated caspase-3. The CSC-exposed males displayed reduction in sperm motility and fertilizing ability and sired pups with reduced body weight and crown-rump length, and smaller litter size with higher numbers of resorption. This model of CSC exposure demonstrates testicular toxicity and developmental defects in the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    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....

  7. High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring.

    Bahous, Renata H; Jadavji, Nafisa M; Deng, Liyuan; Cosín-Tomás, Marta; Lu, Jessica; Malysheva, Olga; Leung, Kit-Yi; Ho, Ming-Kai; Pallàs, Mercè; Kaliman, Perla; Greene, Nicholas D E; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

    2017-03-01

    Methylenetetrahydrofolate reductase (MTHFR) generates methyltetrahydrofolate for methylation reactions. Severe MTHFR deficiency results in homocystinuria and neurologic impairment. Mild MTHFR deficiency (677C > T polymorphism) increases risk for complex traits, including neuropsychiatric disorders. Although low dietary folate impacts brain development, recent concerns have focused on high folate intake following food fortification and increased vitamin use. Our goal was to determine whether high dietary folate during pregnancy affects brain development in murine offspring. Female mice were placed on control diet (CD) or folic acid-supplemented diet (FASD) throughout mating, pregnancy and lactation. Three-week-old male pups were evaluated for motor and cognitive function. Tissues from E17.5 embryos, pups and dams were collected for choline/methyl metabolite measurements, immunoblotting or gene expression of relevant enzymes. Brains were examined for morphology of hippocampus and cortex. Pups of FASD mothers displayed short-term memory impairment, decreased hippocampal size and decreased thickness of the dentate gyrus. MTHFR protein levels were reduced in FASD pup livers, with lower concentrations of phosphocholine and glycerophosphocholine in liver and hippocampus, respectively. FASD pup brains showed evidence of altered acetylcholine availability and Dnmt3a mRNA was reduced in cortex and hippocampus. E17.5 embryos and placentas from FASD dams were smaller. MTHFR protein and mRNA were reduced in embryonic liver, with lower concentrations of choline, betaine and phosphocholine. Embryonic brain displayed altered development of cortical layers. In summary, high folate intake during pregnancy leads to pseudo-MTHFR deficiency, disturbed choline/methyl metabolism, embryonic growth delay and memory impairment in offspring. These findings highlight the unintended negative consequences of supplemental folic acid. © The Author 2017. Published by Oxford University Press.

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

    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.

  9. Born in an Alien Nest : How Do Social Parasite Male Offspring Escape from Host Aggression?

    Lhomme, P.; Ayasse, M.; Valterová, Irena; Lecocq, T.; Rasmont, P.

    2012-01-01

    Roč. 7, č. 9 (2012), e43053/1-e43053/9 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z40550506 Keywords : cuckoo bumblebees * head extract * male repellent odor Subject RIV: CC - Organic Chemistry Impact factor: 3.730, year: 2012

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

    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.

  11. Maternal Chromium Restriction Leads to Glucose Metabolism Imbalance in Mice Offspring through Insulin Signaling and Wnt Signaling Pathways

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

    2016-01-01

    An adverse intrauterine environment, induced by a chromium-restricted diet, is a potential cause of metabolic disease in adult life. Up to now, the relative mechanism has not been clear. C57BL female mice were time-mated and fed either a control diet (CD), or a chromium-restricted diet (CR) throughout pregnancy and the lactation period. After weaning, some offspring continued the diet diagram (CD-CD or CR-CR), while other offspring were transferred to another diet diagram (CD-CR or CR-CD). At 32 weeks of age, glucose metabolism parameters were measured, and the liver from CR-CD group and CD-CD group was analyzed using a gene array. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were used to verify the result of the gene array. A maternal chromium-restricted diet resulted in obesity, hyperglycemia, hyperinsulinemia, increased area under the curve (AUC) of glucose in oral glucose tolerance testing and homeostasis model assessment of insulin resistance (HOMA-IR). There were 463 genes that differed significantly (>1.5-fold change, p chromium deficiency influences glucose metabolism in pups through the regulation of insulin signaling and Wnt signaling pathways. PMID:27782077

  12. Prenatal exposure to diesel exhaust particles and effect on the male reproductive system in mice

    Hemmingsen, Jette Gjerke; Hougaard, Karin Sørig; Talsness, Chris

    2009-01-01

    In utero exposure to diesel exhaust particles may reduce sperm production in adulthood. We investigated the effect of prenatal exposure to diesel exhaust particles on the male reproductive system and assessed endocrine disruption and regulation of aquaporin expression as possible mechanisms...... of action. Dams inhaled 20 mg/m(3) of diesel exhaust particle standard reference material 2975 (SRM2975) or clean air for 1h/day on day 7-19 during pregnancy. Male offspring were killed on day 170 after birth. The dams that had inhaled SRM2975 delivered offspring, which in adulthood had reduced daily sperm...

  13. Age dynamics of radiosensitivity of offsprings of irradiated and nonirradiated Drosophila males

    Gol'zberg, K.L.; Vorobtsova, I.E.

    1978-01-01

    The average life span of the first generation of descendants of irradiated (F 1 I) and nonirradiated (F 1 C) Drosophila males has been investigated after a single and fractionated exposures at early age. The data obtained are in agreement with the assumption that an aggregate amount of radiation-induced mutations obtained from the exposed parent is responsible for the premature ageing of F 1 I descendants

  14. Effect of gamma irradiation on lifespan and offspring physiology of male drosophila melanogaster

    Hou Jiangyu; Gu Wei; Jiang Fangping; Han Hetong

    2010-01-01

    This study aimed to investigate the effects of γ-rays irradiation on adult longevity and physiological changes in F 1 generation.Male Drosophila melanogaster at 1 ∼ 2 days old were irradiated by γ-rays with doses of 5, 10, 15 and 30 Gy. In all experimental groups, mean lifespan, maximum lifespan and 90% of lethaldeath irradiated flies were reduced(at P 1 generation of irradiated group, body weight increased, but the capacity of physiological stress declined. (authors)

  15. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  16. Yangjing Capsule Ameliorates Spermatogenesis in Male Mice Exposed to Cyclophosphamide

    Hongle Zhao

    2015-01-01

    Full Text Available Yangjing capsule (YC, a traditional Chinese compound herbal preparation, has been proven as an effective drug to improve spermatogenesis in clinical practice. However, its pharmacological mechanisms were not fully clarified. This study was designed to investigate the protective effects of YC on spermatogenesis in the mouse model of spermatogenesis dysfunction induced by cyclophosphamide (CP. The administration of YC significantly increased the epididymal index, sperm count, and sperm motility of model mice. Histopathological changes demonstrated that CP caused obvious structural damage to testis, which were reversed by the administration of YC. Results from TUNEL assay showed that treatment with YC dramatically decreased the apoptosis of spermatogenic cell induced by CP. Moreover, YC treatment could inhibit the mRNA and protein expression of Bax to Bcl-2 and also raised expression of AR at both mRNA and protein levels. These data suggest that YC might ameliorate spermatogenesis in male mice exposed to CP through inhibiting the apoptosis of spermatogenic cell and enhancing the actions of testosterone in spermatogenesis.

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

    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

  18. Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.

    Asimes, AnnaDorothea; Torcaso, Audrey; Pinceti, Elena; Kim, Chun K; Zeleznik-Le, Nancy J; Pak, Toni R

    2017-05-01

    Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-01-01

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  20. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    Ma, Noelle [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Nicholson, Catherine J. [Department of Obstetrics and Gynecology, McMaster University (Canada); Wong, Michael [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Holloway, Alison C. [Department of Obstetrics and Gynecology, McMaster University (Canada); Hardy, Daniel B., E-mail: Daniel.Hardy@schulich.uwo.ca [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Children' s Health Research Institute, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada)

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  1. Early weaning impairs body composition in male mice

    Maria Carolina Borges

    2009-12-01

    Full Text Available This study aimed to evaluate the effect of early weaning on body composition and on parameters related to nutritional status in mice. The experimental group consisted of male Swiss Webster mice that were weaned early (at postnatal day fourteen and fed an appropriate diet for growing rodents until postnatal day twenty-one (EW group. The control group consisted of male mice breastfed until postnatal day twenty-one (CON group. All animals were sacrificed on the twenty-first day of life. The EW group showed a decrease in liver and muscle protein content and concentration, brain protein concentration, brain DNA content and concentration, as well as liver and muscle protein/RNA ratio (pO presente estudo objetivou avaliar o efeito do desmame precoce sobre a composição corporal e sobre parâmetros indicativos do estado nutricional de camundongos. O grupo experimental consistiu de camundongos Swiss Webster, machos, desmamados precocemente (14º dia de vida e alimentados com ração apropriada para roedores em crescimento até o 21º dia pós-natal (grupo DESM. O grupo controle consistiu de camundongos amamentados até o 21º dia pós-natal (grupo CON. Todos os animais foram sacrificados no 21º dia de vida. O grupo DESM apresentou redução da concentração e conteúdo hepático e muscular de proteínas, da concentração cerebral de proteínas, da concentração e conteúdo cerebral de DNA e da razão proteína/RNA hepática e muscular (p<0,05. Quanto à composição corporal, o grupo DESM apresentou maior conteúdo de umidade, maior percentual de umidade e lipídios e menor conteúdo e percentual de cinzas e proteína na carcaça (p<0,05. Os resultados indicam que o desmame precoce acarreta em prejuízo à composição corporal e a parâmetros indicativos do estado nutricional, o que pode estar relacionado ao retardo do processo de maturação química. Os dados do presente estudo podem contribuir para o entendimento da influência da alimenta

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

    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,

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

    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,

  4. Hypocalcaemia, Hypoglycaemia, Macrosomia and Congenital Cryptorchidism in a Male Offspring of a Mother with Overweight and Gestational Diabetes Mellitus

    Onyiriuka Alphonsus N.

    2016-12-01

    Full Text Available This paper reports a case of a male infant born to a 32-year-old multiparous mother with overweight (BMI 28.5kg/m2 and gestational diabetes mellitus (GDM. The mother had fasting hyperglycaemia (range 5.7- 6.0mmol/L noted at 24 weeks of pregnancy and was managed with diet alone. There is no family history of diabetes mellitus and the mother did not have pre-eclampsia. Physical examination of the infant revealed macrosomia (birthweight, 4600g and bilateral congenital cryptorchidism. The baby suffered severe hypoglycaemia (blood glucose 1.7mmol/L and hypocalcaemia (total serum calcium 1.03mmol/L, manifesting with seizures. He was successfully managed with 10% dextrose water and calcium gluconate infusion, using standard protocol. His karyotype is 46 XY. The patient was discharged from admission at the age of 10 days and was referred to the paediatric endocrinologist at the tertiary hospital. By 8 weeks of age, the right testis was noticed to have descended into the right scrotum. At the age of 3 months, the left testis was still not palpable either in the inguinal canal or the scrotal sac. The patient was lost to follow up. Conclusion: Diet-treated maternal overweight in association with GDM could potentially increase the risk for hypocalcaemia, hypoglycaemia, macrosomia and congenital cryptorchidism in the offspring, highlighting the need for physicians to assess for the presence of these morbidities in such infants.

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

    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.

  6. Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure.

    Zhang, Lu; Zhang, Zhenzhen; Wang, Feng; Tian, Xiuzhi; Ji, Pengyun; Liu, Guoshi

    2017-10-02

    Embryo implantation is crucial for animal reproduction. Unsuccessful embryo implantation leads to pregnancy failure, especially in human-assisted conception. Environmental factors have a profound impact on embryo implantation. Because people are being exposed to more light at night, the influence of long-term light exposure on embryo implantation should be explored. The effects of long photoperiodic exposure and melatonin on embryo implantation and offspring growth were examined. Long photoperiodic exposure (18:6 h light:dark) was selected to resemble light pollution. Melatonin (10 -2 , 10 -3 , 10 -4 , 10 -5  M) was added to the drinking water of mice starting at Day 1 (vaginal plugs) until delivery. Melatonin treatment (10 -4 ,10 -5  M) significantly increased litter sizes compared to untreated controls (12.9 ± 0.40 and 12.2 ± 1.01 vs. 11.5 ± 0.43; P melatonin (10 -4  M) was selected for further investigation. No remarkable differences were found between melatonin-treated mice and controls in terms of the pups' birth weights, weaning survival rates, and weaning weights. Long photoperiodic exposure significantly reduced the number of implantation sites in treated mice compared to controls (light/dark, 12/12 h), and melatonin rescued this negative effect. Mechanistic studies revealed that melatonin enhanced the serum 17β-estradiol (E 2 ) levels in the pregnant mice and upregulated the expression of the receptors MT1 and MT2 and p53 in uterine tissue. All of these factors may contribute to the beneficial effects of melatonin on embryo implantation in mice. Melatonin treatment was associated with beneficial effects in pregnant mice, especially those subjected to long photoperiodic exposure. This was achieved by enhanced embryo implantation. At the molecular level, melatonin administration probably increases the E 2 level during pregnancy and upregulates p53 expression by activating MT1/2 in the uterus. All of the changes may improve the

  7. Contribution of Myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring

    Hua YUE; Miao LI; Yu-juan LIU; Song-hua WU; Zhen-lin ZHANG; Jin-wei HE; Hao ZHANG; Chun WANG; Wei-wei HU; Jie-mei GU; Yao-hua KE; Wen-zhen FU; Yun-qiu HU

    2012-01-01

    Myostatin gene is a member of the transforming growth factor-β (TGF-β) family that negatively regulates skeletal muscle growth.Genetic polymorphisms in Myostatin were found to be associated with the peak bone mineral density (BMD) in Chinese women.The purpose of this study was to investigate whether Myostatin played a role in the normal variation in peak BMD,lean mass (LM),and fat mass (FM) of Chinese men.Methods:Four hundred male-offspring nuclear families of Chinese Han ethnic group were recruited.Anthropometric measurements,includingthe peak BMD,body LM and FM were measured using dual-energy X-ray absorptiometry (DXA).The single nucleotide polymorphisms (SNPs) studied were tag-SNPs selected by sequencing.Both rs2293284 and +2278G>A were genotyped using TaqMan assay,and rs3791783 was genotyped with PCR-restriction fragment length polymorphism (RFLP) analysis.The associations of the SNPs with anthropometfic variations were analyzed using the quantitative transmission disequilibrium test (QTDT).Results:Using QTDT to detect within-family associations,neither single SNP nor haplotype was found to be associated with peak BMD at any bone site.However,rs3791783 was found to be significantly associated with fat mass of the trunk (P<0.001).Moreover,for within-family associations,haplotypes AGG,AAA,and TGG were found to be significantly associated with the trunk fat mass (all P<0.001).Conclusion:Our results suggest that genetic variation within Myostatin may play a role in regulating the variation in fat mass in Chinese males.Additionally,the Myostatin gene may be a candidate that determines body fat mass in Chinese men.

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

    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.

  9. Strain-specific aggressive behavior of male mice submitted to different husbandry procedures

    Loo, P.L.P. van; Meer, E. van der; Kruitwagen, C.L.J.J.; Koolhaas, J.M.; Zutphen, L.F.M. van; Baumans, V.

    Severe aggression within groups of male laboratory mice can cause serious welfare problems. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study,

  10. Modulation of aggression in male mice : Influence of cage cleaning regime and scent marks

    Van Loo, PLP; Kruitwagen, CLJJ; Van Zutphen, LFM; Koolhaas, JM; Baumans, [No Value

    Group housing of male laboratory mice often leads to welfare problems due to aggressive behaviour. From a welfare perspective, individual housing is not a preferred solution to these problems - and so we sought other ways of reducing aggression between male mice. Aggression peaks after disturbances

  11. An Exercise‐Only Intervention in Obese Fathers  Restores Glucose and Insulin Regulation in  Conjunction with the Rescue of Pancreatic Islet Cell  Morphology and MicroRNA Expression in Male  Offspring

    Nicole O. McPherson

    2017-02-01

    Full Text Available Paternal obesity programs metabolic syndrome in offspring. Low‐impact exercise in obese  males improves the metabolic health of female offspring, however whether this occurred in male  offspring remained unknown. C57BL/6NHsd (Harlan mice were fed a control diet (CD; 6% fat, n =  7 or a high‐fat diet (HFD; 21% fat, n = 16 for 18 weeks. After 9 weeks, HFD‐fed mice either remained  sedentary (HH, n = 8 or undertook low–moderate exercise (HE, n = 8 for another 9 weeks. Male  offspring were assessed for glucose/insulin tolerance, body composition, plasma lipids, pancreatic  islet cell morphology and microRNA expression. Founder HH induced glucose intolerance, insulin  insensitivity, and hyperlipidaemia in male offspring (p < 0.05. Metabolic health was fully restored  in male offspring by founder exercise to control levels. Founder HH reduced pancreatic β‐cell area  and islet cell size in male offspring, and altered the expression of 13 pancreatic microRNAs (p <  0.05. Founder HE led to partial restoration of pancreatic islet cell morphology and the expression  of two pancreatic microRNAs (let7d‐5p, 194‐5p in male offspring. Founder HE reduced male  offspring adiposity, increased muscle mass, reduced plasma free fatty acids (FFAs, and further  altered pancreatic microRNAs (35 vs. HH; 32 vs. CD (p < 0.05. Low‐impact exercise in obese fathers  prior to conception, without dietary change, may be a viable intervention strategy to reduce the illeffects of obesity‐induced paternal programming in male offspring.

  12. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

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

    You-Lin Tain

    2018-04-01

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

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

    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.

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

    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...

  16. Paternal irradiation perturbs the expression of circadian genes in offspring

    Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E.

    2015-01-01

    Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies

  17. Paternal irradiation perturbs the expression of circadian genes in offspring

    Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E., E-mail: yed2@le.ac.uk

    2015-05-15

    Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies.

  18. Effect of Maternal Administration of Edible Bird’s Nest on the Learning and Memory Abilities of Suckling Offspring in Mice

    Yong Xie

    2018-01-01

    Full Text Available Although human brains continue developing throughout the underage developmental stages, the infancy period is considered the most important one for the whole life. It has been reported that sialic acid from edible bird’s nest (EBN can facilitate the development of brain and intelligence. In this study, by oral administration of EBN to female mice during the pregnancy or lactation period, the effects of EBN on the levels of sialic acid in mouse milk were determined using high-performance liquid chromatography (HPLC. Furthermore, the spatial learning performances of their offspring were assessed using the Morris water maze test. Additionally, cerebral malondialdehyde (MDA, superoxide dismutase (SOD, choline acetyltransferase (ChAT, and acetylcholinesterase (AChE in cubs nursed by the female mice given the EBN homogenate were examined, while BDNF immunohistochemical staining and neuron count in hippocampi were investigated as well. These results showed that administration with EBN in maternal mice during pregnancy or lactation period can improve the learning and memory functions in their offspring, possibly by increasing the activities of SOD and ChAT and, at the meantime, decreasing the levels of MDA and activities of AChE. Moreover, BDNF levels for CA1, CA2, and CA3 regions in hippocampi and the numbers of dyed neurons in CA1, CA2, CA3, and DG regions among the offspring were significantly enhanced due to the intake of EBN by the maternal mice. We concluded that maternal administration of EBN during the pregnancy and lactation periods can improve the spatial learning performances in the offspring.

  19. The neuropsychopharmacological effects of Catha edulis in mice offspring born to mothers exposed during pregnancy and lactation.

    Bedada, Worku; Engidawork, Ephrem

    2010-02-01

    Chewing fresh leaves of the khat plant (Catha edulis Forsk) is a deep rooted and widespread habit in East Africa and the Middle East. Although a body of knowledge exists about the adverse effects of khat during pregnancy, data are sparse with regard to the consequences of long-term exposure during pregnancy and lactation. The present work, therefore, was initiated to evaluate the neuropsychopharmacological effects of Catha edulis exposure during pregnancy and lactation in mice at postnatal day 28. To this effect, a lyophilized extract of khat (100 mg/kg, K100 and 200 mg/kg, K200), amphetamine (1 mg/kg, positive control, AMP), and a similar volume of 2% v/v Tween-80 in distilled water (negative control, CONT) were administered daily to pregnant mice from gestational day 6 until weaning. Neuropsychopharmacological measurements were done by making use of a battery of neurobehavioural and cognitive tests. Moreover, toxicity to liver and kidney was also evaluated by determining biochemical markers for possible tissue damage. K200 produced significant motor in-coordination and emotional instability; as revealed by impairment in both cliff avoidance (p learning and the recall tests was observed with K200 and AMP. By contrast, both doses of khat and AMP equally affected performance in the Y-maze (p < 0.05). Alterations in the biochemical indices of liver and kidney function were also noted with AMP and K200. These findings indicate that khat exposure produces dose-related central and peripheral effects during pregnancy and lactation which might pose a serious impediment to the physical and mental development of the offspring. (c) 2009 John Wiley & Sons, Ltd.

  20. Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation.

    Melo, Arine M; Benatti, Rafaela O; Ignacio-Souza, Leticia M; Okino, Caroline; Torsoni, Adriana S; Milanski, Marciane; Velloso, Licio A; Torsoni, Marcio Alberto

    2014-05-01

    The goal of this study was to determine the presence early of markers of endoplasmic reticulum stress (ERS) and insulin resistance in the offspring from dams fed HFD (HFD-O) or standard chow diet (SC-O) during pregnancy and lactation. To address this question, we evaluated the hypothalamic and hepatic tissues in recently weaned mice (d28) and the hypothalamus of newborn mice (d0) from dams fed HFD or SC during pregnancy and lactation. Body weight, adipose tissue mass, and food intake were more accentuated in HFD-O mice than in SC-O mice. In addition, intolerance to glucose and insulin was higher in HFD-O mice than in SC-O mice. Compared with SC-O mice, levels of hypothalamic IL1-β mRNA, NFκB protein, and p-JNK were increased in HFD-O mice. Furthermore, compared with SC-O mice, hypothalamic AKT phosphorylation after insulin challenge was reduced, while markers of ERS (p-PERK, p-eIF2α, XBP1s, GRP78, and GRP94) and p-AMPK were increased in the hypothalamic tissue of HFD-O at d28 but not at d0. These damages to hypothalamic signaling were accompanied by increased triglyceride deposits, activation of NFκB, p-JNK, p-PERK and p-eIF2α. These point out lactation period as maternal trigger for metabolic changes in the offspring. These changes may occur early and quietly contribute to obesity and associated pathologies in adulthood. Although in rodents the establishment of ARC neuronal projections occurs during the lactation period, in humans it occurs during the third trimester. Gestational diabetes and obesity in this period may contribute to impairment of energy homeostasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Offspring Protection

    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.

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

    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.

  3. Effect of breastfeeding piperine on the learning of offspring mice: interaction with caffeine and diazepam.

    Moghadamnia, Ali Akbar; Zangoori, Vahid; Zargar-Nattaj, Seyed Sadegh; Tayebi, Pooya; Moghadamnia, Yasaman; Jorsaraei, Seyed Gholam Ali

    2010-01-01

    Piperine, the main alkaloid of black pepper (Piper nigrum), has been suggested to display several pharmacological properties, including pain relief, anticonvulsant, antidepressant-like, antianxiety, sedative, and anti-inflammatory effects. This study was designed to investigate the effect of piperine on learning in mice and the interaction of the effect with caffeine and diazepam. Piperine (100 mg/kg intraperitoneally) was injected into the mouse mothers or nursing dams during breastfeeding for 25 days at five-day intervals. After feeding the newborn mice, their learning was evaluated using a step-through passive avoidance task. Mouse learning was assessed 1 hr and 24 hr and 1 week after a training session. Piperine increased learning in the first (1 hr: 243.33 s vs 55.17 s, P = 0.002) and third assessments (1 week: 226 s vs 97 s, P effect of a low dose of caffeine (25 mg/kg intraperitoneally after a shock of 2 s duration) in a first assessment (295.17 s vs 149.17 s, P = 0.026) compared to a higher dose of caffeine. Piperine reversed diazepam (1 mg/kg intraperitoneally) suppression of learning 24 hours after training by a 4 s shock (298 s vs 135.67 s, P = 0.03). According to the results, piperine alone significantly increased learning 1 hour and 1 week after training assessments, and learning can be improved in the short term when followed by piperine administration. It was also shown that piperine can potentiate the effect of a low dose of caffeine and can reverse the effect of diazepam.

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

    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.

  5. Brain serotonin signaling does not determine sexual preference in male mice.

    Mariana Angoa-Pérez

    Full Text Available It was reported recently that male mice lacking brain serotonin (5-HT lose their preference for females (Liu et al., 2011, Nature, 472, 95-100, suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO and the main olfactory epithelium (MOE. Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2, which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female or animate (male or female mouse in estrus sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference.

  6. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

    Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2017-07-07

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

  7. Maternal allergen immunisation to prevent sensitisation in offspring: Th2-polarising adjuvants are more efficient than a Th1-polarising adjuvant in mice

    Melkild Ingrid

    2010-03-01

    Full Text Available Abstract Background Allergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. We investigated the capacity for allergic sensitisation in offspring after induction of a Th1- or a Th2-polarised immune response to the same allergen in mothers during pregnancy. Results During pregnancy, mice were immunised with ovalbumin (OVA given with either one of the Th2-adjuvants pertussis toxin (PT or Al(OH3 (aluminium hydroxide, or with the Th1 adjuvant CpG. Offspring were immunised with OVA in Al(OH3 as young adults. Serum and supernatants from ex vivo stimulated or non-stimulated spleen cells from mothers and offspring were analysed for OVA-specific antibodies and cytokines, respectively. Mothers immunised with OVA together with either Al(OH3 or PT had increased levels of OVA-specific IgE and IgG1 compared to naive mothers, whereas mothers immunised with OVA together with CpG had increased levels of OVA-specific IgG2a compared to naive mothers. In general the highest levels of IL-5, IL-10, and IFNγ were observed in spleen cells from mothers immunised with PT and OVA. Upon immunisation, offspring from mothers immunised with OVA and either PT or Al(OH3 showed reduced levels of OVA-specific IgE and IgG1 and increased levels of OVA-specific IgG2a antibodies compared to offspring from naive mothers. Maternal immunisation with CpG and OVA did not affect antibody responses in offspring. Conclusion Allergic sensitisation in the offspring was affected by the type of adjuvant used for immunisation of the mothers with the same allergen. Th2 polarisation of the immune response in the mothers was found to give reduced IgE levels upon sensitisation of the offspring, whereas no reduction was achieved with Th1 polarisation in the mothers.

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

    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

  9. Individual variation in paternal responses of virgin male California mice (Peromyscus californicus): behavioral and physiological correlates

    de Jong, T.R.; Korosi, A.; Harris, B.N.; Perea-Rodriguez, J.P.; Saltzman, W.

    2012-01-01

    California mice Peromyscus californicus are a rodent species in which fathers provide extensive paternal care; however, behavioral responses of virgin males toward conspecific neonates vary from paternal behavior to tolerance to infanticide. Indirect evidence suggests that paternal responses might

  10. Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

    Mahbod, Parinaz; Smith, Eric P; Fitzgerald, Maureen E; Morano, Rachel L; Packard, Benjamin A; Ghosal, Sriparna; Scheimann, Jessie R; Perez-Tilve, Diego; Herman, James P; Tong, Jenny

    2018-01-01

    Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent. Copyright © 2018 Endocrine Society.

  11. Behavioural strategies of aggressive and non-aggressive male mice in response to inescapable shock

    Benus, R.F.; Bohus, B.; Koolhaas, J.M.; Oortmerssen, G.A. van

    1990-01-01

    The effect of exposure to inescapable long-duration shocks of moderate intensity on intershock activity and on subsequent escape or avoidance performance was studied in aggressive and non-aggressive male mice. The activity of the non-aggressive mice was severely suppressed during the inescapable

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

    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

  13. Comparison of the course of infection with Giardia muris in male and female mice.

    Daniels, C W; Belosevic, M

    1995-01-01

    The infection with Giardia muris in male and female C57BL/6 mice was characterized by enumerating cyst release in the feces and trophozoite burden in the small intestine. Cyst release differed between males and females during the course of the primary and challenge infections. Males and females released similar numbers of cysts in the feces during the acute phase of the infection. However, the trophozoite burden was significantly higher in males during the same period. Males released cysts in their feces longer than females and trophozoites present in their intestines for a longer period than females. From day 18 of infection the females did not release cysts in their feces, while males continued to do so for at least 60 days. Thus, distinct differences exist between male and female mice in their ability to harbor and eliminate this intestinal parasite.

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

    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 ...

  15. Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice

    Callewaert, F.; Bakker, A.; Schrooten, J.; Van Meerbeek, B.; Verhoeven, G.; Boonen, S.; Vanderschueren, D.

    2010-01-01

    In female mice, estrogen receptor-alpha (ERα) mediates the anabolic response of bone to mechanical loading. Whether ERα plays a similar role in the male skeleton and to what extent androgens and androgen receptor (AR) affect this response in males remain unaddressed. Therefore, we studied the

  16. The role of p38 in mitochondrial respiration in male and female mice.

    Ju, Xiaohua; Wen, Yi; Metzger, Daniel; Jung, Marianna

    2013-06-07

    p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38(loxP/loxP) mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Effect of Fenbendazole on Three Behavioral Tests in Male C57BL/6N Mice

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-01-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of...

  18. Dominant lethal mutations in male mice fed γ-irradiated diet

    Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

    1975-01-01

    Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

  19. Polybrominated Diphenyl Ethers Orally Administration to Mice Were Tansferred to Offspring during Gestation and Lactation with Disruptions on the Immune System.

    Hong, Soon Keun; Sohn, Kyung Hee; Kim, In Young; Lee, Jong Kwon; Ju, Jung Hun; Kim, Jin Ho; Lim, Chae Hyung; Han, Beom Seok; Jung, Hwa Chul; Lee, Jin Yong; Park, Kui Lea

    2010-04-01

    The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.

  20. Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

    Ramesh Chennupati

    Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

  1. Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population

    Jensen, Tina Kold; Jørgensen, Niels; Asklund, Camilla

    2007-01-01

    motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a lower serum testosterone level and free androgen index (results not statistically significant). These findings should be viewed in light of the increasing use of fertility......Little is known the about the reproductive health of offspring after fertility treatment. In 2001-2005, the authors approached young Danish men attending a compulsory physical examination to determine their fitness for military service. A total of 1,925 men volunteered, delivered a semen sample...

  2. Effects of leached components from a hybrid resin composite on the reproductive system of male mice

    Taher Akbari Saeed

    2012-01-01

    Full Text Available Background and Aims: There is concern that leached components from dental composites may cause adverse changes in the reproductive health. This study aimed to assess the effects of leached components from a hybrid resin composite on the reproductive system of male mice.Materials and Methods: In the present animal study, twenty adult Syrian male mice were divided into two groups of 10 mice each. In the test group, components which leached from samples made from Filtek Z250 resin composite into 75% ethanol were daily administered to the mice for 28 days. In the control group, the procedure was repeated in the same way as the test group but without placing composite samples in the solution. Then, the body weight, weights of paired testes, Gonado Somatic Index, sperm viability, sperm motility, epididymal sperm reserve and daily sperm production were recorded. Four male mice in each group were mated with untreated female mice for 10 days. After that, the number of pregnant females and number of infants were recorded. The data were analyzed using repeated measures ANOVA, Chi-square test and t-test.Results: There was a significant reduction in the sperm viability and sperm motility of male mice in the test group compared to the control group (P=0.001. There was no any significant differences in other parameters between two groups (P>0.05.Conclusion: This study showed that the leached components from resin composites cannot cause infertility but they could potentially cause some adverse effects on the reproductive system of male mice.

  3. Carcinogenesis in C57BL mice after multigeneration exposure of the male germinal line to tritium

    Mewissen, D.J.; Ugarte, A.S.; Rust, J.J.

    1986-01-01

    The occurrence of a heritable, multiple intestinal adenocarcinoma (HMIA) was observed in the offspring of an outcross between a male (or female) parent originating from our C57 Black/6M strain and his female (or male) mating counterpart originating from an experimental subline of the same strain, propagated with multigeneration exposure of the male parent to low-level tritium. Multiple intestinal malignancy was observed with a high-expression frequency in all animals examined in five subsequent generations, irrespective of the sex of the initial ascendant originating from the experimental subline, exposed to tritiated water. A digenic inheritance with partial penetrance is postulated, involving at least a two-stage process of tumorigenesis, namely, a dominant mutation at one locus and a second mutation to a recessive which, as long as it remained homozygous, prevented expression of the tumorigenic dominant gene. 10 refs., 2 tabs

  4. Male mice song syntax depends on social contexts and influences female preferences

    Jonathan eChabout

    2015-04-01

    Full Text Available In 2005 Holy & Guo advanced the idea that male mice produce ultrasonic vocalizations (USV with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for.

  5. Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

    Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

    2018-04-02

    Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Male mice with deleted Wolframin (Wfs1 gene have reduced fertility

    Aunapuu Marina

    2009-08-01

    Full Text Available Abstract Background Wolfram Syndrome (WS is an autosomal recessive disorder characterised by non-autoimmune diabetes mellitus, optic atrophy, cranial diabetes insipidus and sensorineural deafness. Some reports have described hypogonadism in male WS patients. The aim of our study was to find out whether Wfs1 deficient (Wfs1KO male mice have reduced fertility and, if so, to examine possible causes. Methods Wfs1KO mice were generated by homologous recombination. Both Wfs1KO and wild type (wt male mice were mated with wt female mice. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analysed. Serum testosterone and FSH concentrations were also measured. Results The pregnancy rate in wt females mated with Wfs1KO males was significantly lower than in the control group (15% vs. 32%; p Conclusion The impaired fertility of Wfs1KO male mice is most likely due to changes in sperm morphology and reduced number of spermatogenic cells. The exact mechanism through which the Wfs1 gene influences sperm morphology needs to be clarified in further studies.

  7. Impairment of object recognition memory by maternal bisphenol A exposure is associated with inhibition of Akt and ERK/CREB/BDNF pathway in the male offspring hippocampus.

    Wang, Chong; Li, Zhihui; Han, Haijun; Luo, Guangying; Zhou, Bingrui; Wang, Shaolin; Wang, Jundong

    2016-02-03

    Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9-20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index=the time spent exploring the novel object/(the time spent exploring the novel object+the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho-Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that

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

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

    2015-01-01

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

  9. Dopamine D5 receptor modulates male and female sexual behavior in mice.

    Kudwa, A E; Dominguez-Salazar, E; Cabrera, D M; Sibley, D R; Rissman, E F

    2005-07-01

    Dopamine exerts its actions through at least five receptor (DAR) isoforms. In female rats, D5 DAR may be involved in expression of sexual behavior. We used a D5 knockout (D5KO) mouse to assess the role of D5 DAR in mouse sexual behavior. Both sexes of D5KO mice are fertile and exhibit only minor disruptions in exploratory locomotion, startle, and prepulse inhibition responses. This study was conducted to characterize the sexual behavior of male and female D5KO mice relative to their WT littermates. Female WT and D5KO littermates were ovariectomized and given a series of sexual behavior tests after treatment with estradiol benzoate (EB) and progesterone (P). Once sexual performance was optimal the dopamine agonist, apomorphine (APO), was substituted for P. Male mice were observed in pair- and trio- sexual behavior tests. To assess whether the D5 DAR is involved in rewarding aspects of sexual behavior, WT and D5KO male mice were tested for conditioned place preference. Both WT and D5KO females can display receptivity after treatment with EB and P, but APO was only able to facilitate receptivity in EB-primed WT, not in D5KO, mice. Male D5KO mice display normal masculine sexual behavior in mating tests. In conditioned preference tests, WT males formed a conditioned preference for context associated with either intromissions alone or ejaculation as the unconditioned stimulus. In contrast, D5KO males only showed a place preference when ejaculation was paired with the context. In females, the D5 DAR is essential for the actions of dopamine on receptivity. In males, D5 DAR influences rewarding aspects of intromissions. Taken together, the work suggests that the D5 receptor mediates dopamine's action on sexual behavior in both sexes, perhaps via a reward pathway.

  10. Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

    Sara H Windahl

    Full Text Available Androgens are important regulators of bone mass but the relative importance of testosterone (T versus dihydrotestosterone (DHT for the activation of the androgen receptor (AR in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2, encoded by separate genes (Srd5a1 and Srd5a2. 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05 and cortical bone mineral content (-15%, p<0.05 but unchanged serum androgen levels compared with wild type (WT mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05 in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05. Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

  11. A Maternal Gluten-Free Diet Reduces Inflammation and Diabetes Incidence in the Offspring of NOD Mice

    Hansen, Camilla Hartmann Friis; Krych, Lukasz; Buschard, Karsten

    2014-01-01

    a pronounced difference between both mothers and their offspring on different diets, characterized by increased numbers of Akkermansia, Proteobacteria, and TM7 in the GF diet group. In addition, pancreatic forkhead box P3 regulatory T cells were increased in GF-fed offspring, as were M2 macrophage gene markers...... and tight junction-related genes in the gut, while intestinal gene expression of proinflammatory cytokines was reduced. An increased proportion of T cells in the pancreas expressing the mucosal integrin alpha 4 beta 7 suggests that the mechanism involves increased trafficking of gut-primed immune cells...

  12. Effect of Vomeronasal Organ Removal From Male Mice on Their Preference for and Neural Fos Responses to Female Urinary Odors

    Pankevich, Diana E.; Cherry, James A.; Baum, Michael J.

    2006-01-01

    Four experiments were conducted to determine whether vomeronasal organ (VNO) inputs in male mice mediate the rewarding properties of estrous female urinary odors. Sexually naive male mice with either an intact (VNOi) or lesioned (VNOx) VNO preferred to investigate female urine over water in Y-maze tests. Subsequently, VNOi males ran significantly more quickly and remained in nasal contact longer with estrous female urine than with male urine, whereas VNOx males investigated these odors equall...

  13. Quinine controls body weight gain without affecting food intake in male C57BL6 mice

    Cettour-Rose Philippe

    2013-02-01

    Full Text Available Abstract Background Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5. Results Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice. Conclusion Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.

  14. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  15. Juvenile spermatogonial depletion (jsd): a genetic defect of germ cell proliferation of male mice.

    Beamer, W G; Cunliffe-Beamer, T L; Shultz, K L; Langley, S H; Roderick, T H

    1988-05-01

    Adult C57BL/6J male mice homozygous for the mutant gene, juvenile spermatogonial depletion (jsd/jsd), show azoosper4ia and testes reduced to one-third normal size, but are otherwise phenotypically normal. In contrast, adult jsd/jsd females are fully fertile. This feature facilitated mapping the jsd gene to the centromeric end of chromosome 1; the gene order is jsd-Isocitrate dehydrogenase-1 (Idh-1)-Peptidase-3 (Pep-3). Analysis of testicular histology from jsd/jsd mice aged 3-10 wk revealed that these mutant mice experience one wave of spermatogenesis, but fail to continue mitotic proliferation of type A spermatogonial cells at the basement membrane. As a consequence, histological sections of testes from mutant mice aged 8-52 wk showed tubules populated by modest numbers of Sertoli cells, with only an occasional spermatogonial cell. Some sperm with normal morphology and motility were observed in epididymides of 6.5- but not in 8-wk or older mutants. Treatment with retinol failed to alter the loss of spermatogenesis in jsd/jsd mice. Analyses of serum hormones of jsd/jsd males showed that testosterone levels were normal at all ages--a finding corroborated by normal seminal vesicle and vas deferens weights, whereas serum follicle-stimulating hormone levels were significantly elevated in mutant mice from 4 to 20 wk of age. We hypothesize the jsd/jsd male may be deficient in proliferative signals from Sertoli cells that are needed for spermatogenesis.

  16. Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

    Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

    2017-11-01

    Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

  17. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.

    Chen, Yongmei; Wang, Huizhen; Qi, Nan; Wu, Hui; Xiong, Weipeng; Ma, Jing; Lu, Qingxian; Han, Daishu

    2009-10-01

    Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

  18. Dominant lethal tests of male mice given 239Pu salt injections

    Luening, K.G.; Froelen, H.; Nilsson, A.

    1976-01-01

    To study the possible genetic effects of 239 Pu manifesting in dominant lethals, five test series (E1-E5) were performed. Males from an inbred CBA strain were given 239 Pu salt injections intravenously and mated weekly to 3 CBA females each for 12 to 24 weeks. Some interruptions in the mating scheme were made. For the first two test series (E1, E2) 239 Pu nitrate solution and 239 Pu citrate, used in E3-E5, were prepared. The solution was millipore filtered just prior to injection. Among a total of 10255 implants sired by males given Pu-nitrate in E1 and E2 no significant excess of intra-uterine death relative to 7216 control implants occurred. Test series E3-E5 with 60 males each, used three groups of 20, with one control group. In E3, 0.5 μCi and 0.1 μCi were given per male/group, respectively; in E4 and E5, 0.25 μCi and 0.05 μCi, respectively. The males given 0.5 μCi in E3 became successively sterile from the 7th week. The results in E3-E5 point in the same direction with significant excess of intra-uterine death in E3 and E5. In E4 the females from matings from the 9th, 14th and 16th week, and in E5 females from the 9th week, were allowed to litter to give F 1 offspring. Dominant lethal tests of F 1 males gave concordant results in all four samples, showing significantly excessive death in offspring to F 1 males whose fathers had received Pu. The excessive death was evenly distributed and did not indicate the presence of semisterile F 1 males. In tests of Pu-injected males and of F 1 males a remarkable excess of death in late stages of foetal development was observed. Such effects had never before been observed in this CBA strain in tests of extrinsic and intrinsic exposure to ionizing irradiation

  19. Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice.

    Desroziers, Elodie; Brock, Olivier; Bakker, Julie

    2017-04-01

    We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during development, inducing both a male-and female-typical pattern of PR expression in the mouse hypothalamus. In the present study, we took advantage of a newly developed PR antagonist (ZK 137316) to determine whether PR contributes to either male- or female-typical sexual differentiation. Thus groups of male and female C57Bl/6j mice were treated with ZK 137316 or OIL as control: males were treated neonatally (P0-P10), during the critical period for male sexual differentiation, and females were treated prepubertally (P15-P25), during the critical period for female sexual differentiation. In adulthood, mice were tested for sexual behavior. In males, some minor effects of neonatal ZK treatment on sexual behavior were observed: latencies to the first mount, intromission and ejaculation were decreased in neonatally ZK treated males; however, this effect disappeared by the second mating test. By contrast, female mice treated with ZK during the prepubertal period showed significantly less lordosis than OIL-treated females. Mate preferences were not affected in either males or females treated with ZK during development. Taken together, these results suggest a role for PR and thus perhaps progesterone in the development of lordosis behavior in female mice. By contrast, no obvious role for PR can be discerned in the development of male sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Reproductive effects of lipid soluble components of Syzygium aromaticum flower bud in male mice

    Raghav Kumar Mishra

    2013-01-01

    Full Text Available Background: The flower buds of Syzygium aromaticum (clove have been used in indigenous medicines for the treatment of male sexual disorders in Indian subcontinent. Objective: To evaluate the effect of Syzygium aromaticum flower bud on male reproduction, using Parkes (P strain mice as animal model. Materials and Methods: Mice were orally administered lipid soluble components of Syzygium aromaticum flower bud in doses of 15, 30, and 60 mg/kg body weight for 35 days, and several male reproductive endpoints were evaluated. Results: Treatment with lower dose (15 mg of Syzygium increased the motility of sperm and stimulated the secretory activities of epididymis and seminal vesicle, while higher doses (30 and 60 mg had adverse effects on sperm dynamics of cauda epididymidis and on the secretory activities of epididymis and seminal vesicle. Libido was not affected in treated males; however, a significant decrease in litter in females sired by males treated with higher doses of Syzygium was recorded. Conclusion: Treatment with Syzygium aromaticum flower bud causes dose-dependent biphasic effect on male reproductive indices in P mice; lower dose of Syzygium appears stimulatory, while the higher doses have adverse effect on male reproduction. The results suggest that the lower dose of Syzygium may have androgenic effect, but further studies are needed to support this contention.

  1. Spatial learning and memory in male mice with altered growth hormone action.

    Basu, Amrita; McFarlane, Hewlet G; Kopchick, John J

    2017-07-01

    Growth hormone (GH) has a significant influence on cognitive performance in humans and other mammals. To understand the influence of altered GH action on cognition, we assessed spatial learning and memory using a Barnes maze (BM) comparing twelve-month old, male, bovine GH (bGH) and GH receptor antagonist (GHA) transgenic mice and their corresponding wild type (WT) littermates. During the acquisition training period in the BM, bGH mice showed increased latency, traveled longer path lengths and made more errors to reach the target than WT mice, indicating significantly poorer learning. Short-term memory (STM) and long-term memory (LTM) trials showed significantly suppressed memory retention in bGH mice when compared to the WT group. Conversely, GHA mice showed significantly better learning parameters (latency, path length and errors) and increased use of an efficient search strategy than WT mice. Our study indicates a negative impact of GH excess and a beneficial effect of the inhibition of GH action on spatial learning and memory and, therefore, cognitive performance in male mice. Further research to elucidate GH's role in brain function will facilitate identifying therapeutic applications of GH or GHA for neuropathological and neurodegenerative conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Expression of GAT1 in male reproductive system and its effects on reproduction in mice.

    Zhang, JinFu; Gui, YaPing; Yuan, Tao; Bian, CuiDong; Guo, LiHe

    2009-12-01

    The present study was carried out to identify GABA (gamma-aminobutyric acid) transport protein I (GAT1) in male reproductive organs and to study the effect of GAT1 overexpression on the male reproductive system in GAT1 transgenic mice (TG). Expression and location of GAT1 in testes, epididymis, and sperm of wild-type (WT) mice were identified by immunohistochemistry and western-blot. Histological changes of testes, epididymis, and sperm of transgenic mice overexpressing GAT1 were detected by immunofluorenscent staining and haematoxylin and eosin (HE) staining. GAT1 expression was detected in the testes, epididymis, and sperm of non-transgenic mice. Vacuolization and deformity of spermatogenic cells were observed in the transgenic mice, but the epididymis was unremarkable. Immunofluorenscent staining showed that the number of diastrophic and decapitated sperm increased significantly in transgenic mice to 46.9% from 7.3% in nontransgenic mice. These results suggest that abnormal expression of GAT1 could result in spermiogenesis function injury, sperm paramorphia and dysgenesis.

  3. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. © 2016 Society for Endocrinology.

  4. Synaptonemal complex analysis of X-7 translocations in male mice

    Ashley, T. (Univ. of Tennessee, Knoxville); Russell, L.B.; Cacheiro, N.L.A.

    1982-01-01

    The synaptonemal complexes of surface-spread spermatocytes of mice heterozygous for one of two reciprocal translations (R3 and R5) between the X and chromosome 7 have been examined by light and electron microscopy (EM). The break points of R3 were determined to be at 70% of chromosome 7, as measured from the centromere, and at 22% of the X. Translocation quadrivalents were formed almost exclusively. The break points of R5 were at 21% of chromosome 7 as measured from the centromere, and at 83% of the X. There was little indication that the break in the X interfered with sex-chromosome synapis between the 7X and Y. Univalent Y's were not observed in R3, and only seldom observed (8-14%) in R5. However, in contrast to R3, R5 formed quadrivalents relatively rarely (20% in the EM study of 100 nuclei), and hetermorphic bivalents of 7X-Y and X7-7 quite frequently (72%). Possible causes of this high bivalent frequency are discussed. Light-microsope (LM) analysis alone was found to be inadequate for interpreting synaptic configurations (quadrivalents vs. bivalents) in R5. The LM analysis was further complicated by the occurrence of nonhomologous synapsis in the heteromorphic bivalents of R5, a phenomonon easily recognized and interpreted in the EM portion of the study.

  5. Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.

    Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J

    We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.

  6. Chromosome aberrations in F1 from irradiated male mice studied by their synaptonemal complexes

    Kalikinskaya, E.I.; Kolomiets, O.L.; Shevchenko, V.A.; Bogdanov, Yu.F.

    1986-01-01

    Possible implications of surface-spread synaptonemal complex (SC) karyotyping in analysing the causes of sterility of F 1 from irradiated male mice are demonstrated in this work. After irradiation by 137 Cs γ-rays at a dose of 5 Gy the males were mated to unirradiated females and genetic analysis of fertility in the F 1 progeny was carried out. Males with abnormal fertility were examined for the presence of chromosome aberrations in diakinesis-metaphase I and in pachytene by the method of surface-spread SC karyotyping. In most cases, SC karyotyping provides additional information and permits the detection and analysis of aberrations that are not revealed in diakinesis. Two reciprocal translocations, one X autosomal and one nonreciprocal translocation were discovered in five F 1 males studied. It is concluded that the method is efficient in detecting translocations in pachytene in partially fertile F 1 hybrids of irradiated and normal mice. (orig.)

  7. A vasoactive role for endogenous relaxin in mesenteric arteries of male mice.

    Chen Huei Leo

    Full Text Available The peptide hormone relaxin has striking effects on the vascular system. Specifically, endogenous relaxin treatment reduces myogenic reactivity through nitric oxide (NO-mediated vasorelaxation and increases arterial compliance in small resistance arteries. However, less is known about the vascular roles of endogenous relaxin, particularly in males. Therefore, we used male wild-type (Rln+/+ and relaxin knockout (Rln-/- mice to test the hypothesis that passive wall properties and vascular reactivity in mesenteric arteries would be compromised in Rln-/- mice. Passive compliance was determined in arteries (n=8-9 mounted on a pressure myograph and in Ca2+-free Krebs containing 2 mM EGTA. Passive volume compliance was significantly (P=0.01 decreased in the mesenteric arteries of Rln-/- mice. Vascular reactivity was assessed using wire myography. In mesenteric arteries (n=5 of Rln-/- mice, there was a significant (P<0.03 increase in sensitivity to the vasoconstrictors phenylephrine and thromboxane-mimetic U41669. This enhanced responsiveness to vasoconstrictors was abolished by endothelial denudation, and attributed to impaired NO and prostanoid pathways in Rln-/- mice. Sensitivity to the endothelial agonist acetylcholine was significantly (n=7-9, P ≤ 0.03 decreased, and this was abolished in the presence of the cyclooxygenase inhibitor, indomethacin (2 µM. This indicates that prostanoid vasoconstrictor pathways were upregulated in the mesenteric arteries of Rln-/- mice. In summary, we demonstrate endothelial dysfunction and impaired arterial wall remodeling in male mice deficient in relaxin. Thus, our results highlight a role for endogenous relaxin in the maintenance of normal mesenteric artery structure and function in males.

  8. Editor's Highlight: Congener-Specific Disposition of Chiral Polychlorinated Biphenyls in Lactating Mice and Their Offspring: Implications for PCB Developmental Neurotoxicity.

    Kania-Korwel, Izabela; Lukasiewicz, Tracy; Barnhart, Christopher D; Stamou, Marianna; Chung, Haeun; Kelly, Kevin M; Bandiera, Stelvio; Lein, Pamela J; Lehmler, Hans-Joachim

    2017-07-01

    Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of 2 environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8-weeks old) were fed daily, beginning 2 weeks prior to conception and continuing throughout gestation and lactation, with 3.1 µmol/kg bw/d of racemic 2,2',3,5',6-pentachlorobiphenyl (PCB 95) or 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in peanut butter; controls received vehicle (peanut oil) in peanut butter. PCB 95 levels were higher than PCB 136 levels in both dams and pups, consistent with the more rapid metabolism of PCB 136 compared with PCB 95. In pups and dams, both congeners were enriched for the enantiomer eluting second on enantioselective gas chromatography columns. OH-PCB profiles in lactating mice and their offspring were complex and varied according to congener, tissue and age. Developmental exposure to PCB 95 versus PCB 136 differentially affected the expression of P450 enzymes as well as neural plasticity (arc and ppp1r9b) and thyroid hormone-responsive genes (nrgn and mbp). The results suggest that the enantioselective metabolism of PCBs to OH-PCBs may influence neurotoxic outcomes following developmental exposures, a hypothesis that warrants further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Thyroid states regulate subcellular glucose phosphorylation activity in male mice

    Flavia Letícia Martins Peçanha

    2017-07-01

    Full Text Available The thyroid hormones (THs, triiodothyronine (T3 and thyroxine (T4, are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0.25 μg/g, i.p. during 21 days mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, n = 10, gastrocnemius (369.2% ± 112.4, n = 10 and heart (142.2% ± 13.6, n = 10 muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T3 administration (single dose of T3, 1.25 μg/g, i.p. did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T3 treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.

  10. Serum antibody responses by male and female C57Bl/6 mice infected with Giardia muris.

    Daniels, C W; Belosevic, M

    1994-09-01

    We compared the levels of serum antibodies in male and female C57Bl/6 mice during the primary and after challenge infection with Giardia muris. Male mice began passing cysts in their faeces earlier than females, and were shedding cysts for over 60 days, while females stopped shedding cysts by day 20 after infection. In both males and females there were significant increases in parasite-specific IgM 10 and 20 days after infection. No differences in parasite-specific serum IgA were observed until 40 days after infection. Parasite-specific IgG (whole) levels were elevated on days 20 and 40 in females, while males showed no significant increases. In addition, females had a much stronger IgG2b and IgG3 response than males. After challenge with either cysts or soluble parasite protein only the females had significant increases in specific anti-parasite IgG2b. Our data show differential ability of males and females to control the infection with G. muris is paralleled by a difference in the anti-parasite serum IgG response of the mice.

  11. Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice

    Leakey, Julian E.A.; Seng, John E.; Latendresse, John R.; Hussain, Nursreen; Allen, Laura J.; Allaben, William T.

    2003-01-01

    Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F 1 mice in a 2-year bioassay of chloral hydrate. Male B6C3F 1 mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined 'idealized' weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation

  12. The SocioBox: A novel paradigm to assess complex social recognition in male mice

    Dilja Krueger-Burg

    2016-08-01

    Full Text Available Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition memory. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method, we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition memory deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology.

  13. Reproductive performance of male mice after hypothalamic ghrelin administration.

    Poretti, Maria Belen; Frautschi, Camila; Luque, Eugenia Mercedes; Bianconi, Santiago; Martini, Ana Carolina; Stutz, Graciela; Vincenti, Laura Maria; Santillán, María Emilia; Ponzio, Marina Flavia; Schiöth, Helgi; Fiol De Cuneo, Marta Haydee; Carlini, Valeria Paola

    2018-05-23

    It has been demonstrated that food intake and reproductive physiology are both simultaneously modulated to optimize reproductive success under fluctuating metabolic conditions. Ghrelin (Ghr) is an orexigenic peptide identified as the endogenous ligand of the growth hormone secretagogue receptor that is being investigated for its potential role on reproduction. Considering that data available so far are still limited and characterization of Ghr action mechanism on the reproductive system has not been fully elucidated, we studied the hypothalamus participation in Ghr effects on sperm functional activity, plasma levels of gonodotropins and histological morphology in mice testes after hypothalamic infusion of 0.3 or 3.0 nmol/day Ghr or artificial cerebrospinal fluid (ACSF) at different treatment periods. We found that Ghr 3.0 nmol/day administration for 42 days significantly reduced sperm concentration (Ghr 3.0 nmol/day=14.05±2.44 x106/ml vs. ACSF=20.33±1.35 x106/ml, p< 0.05) and motility (Ghr 3.0 nmol/day=59.40±4.20% vs. ACSF=75.80±1.40%, p< 0.05). In addition, histological studies showed a significant decrease percentage of spermatogonia (Ghr 3.0 nmol/day=6,76±0,68% vs. ACSF=9,56±0,41%, p< 0.05) and sperm (Ghr 3.0 nmol/day=24,24±1,92% vs. ACSF=31,20±3,06%, p< 0.05). These results were associated with a significant reduction in luteinizing hormone and testosterone plasma levels (p<0.05). As Ghr is an orexigenic peptide, body weight and food intake were measured. Results showed that Ghr increases both parameters; however, the effect did not last beyond the first week of treatment. Results presented in this work confirm that central Ghr administration impairs spermatogenesis and suggest that this effect is mediated by inhibition of hypothalamic-pituitary-gonadal axis.

  14. Female scent signals enhance the resistance of male mice to influenza.

    Ekaterina A Litvinova

    Full Text Available BACKGROUND: The scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating. METHODS AND FINDINGS: We propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice. CONCLUSIONS: Our data provide the first demonstration of the adaptive immunological response to female odor stimuli through induction of nonspecific immune responses in the upper respiratory tract.

  15. Histological and Physiological Alterations Induced by Thermal Neutron Fluxes in Male Swiss Albino Mice

    Alzergy, A.A.; Emara, N.M.; Abd El-Latif, A.A.; El-Saady, S.M.M.; Emara, N.M.; Abd El-Latif, A.A.

    2010-01-01

    This work was performed to investigate the biological effects of different thermal neutron fluxes (0.27x10 8 , 0.52X10 8 , 1.089X10 8 , 2.16X10 8 and 4.32X10 8 ) on liver and kidney of male mice using neutron irradiation cell with Ra-Be(α,n) 3 mCi neutron source Leybold (55930). Exposed to various fluxes of thermal neutron induced a dramatic alterations in hepatic and renal functions as indicated by biochemical estimation of several parameters (bilirubin, SGT, and alkaline phosphate .Urea , total protein, and albumin) and confirmed by histological examinations Thermal neutron exposure induces marked increase in the serum activities of total bilirubin, alanine amino transaminase (ALT or GPT), and alkaline phosphate, whereas, urea, total protein and albumin showed marked decline as compared to control group. The physiological changes induced in thermal neutron fluxes dependent manner. Histopathological results revealed mild to severe type of necrosis, and degenerative changes in liver and kidney of male mice exposed to thermal neutron fluxes. Also it was found that the histopathological alterations induced in thermal neutron fluxes dependent manner. It was found that exposed to thermal neutron fluxes irradiation plays prominent role in the development of the physiological alterations in male Swiss albino mice. The Former up normalities as a result of the sequence events followed interaction of radiation with the former biological mater (liver and kidney) of male Swiss albino mice, which are, physical, physicochemical, chemical, and biological stages.

  16. Behavioral profiles of genetically selected aggressive and nonaggressive male wild house mice in two anxiety tests

    Hogg, S; Wurbel, H; Steimer, T; de Ruiter, A; Koolhaas, J; Sluyter, F; Driscoll, Peter

    2000-01-01

    Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice were tested in a hexagonal tunnel maze and light-dark preference (LD) box to determine if the bidirectional selection for aggressive behavior leads to a coselection for different levels of trait anxiety. The tunnel maze

  17. Genotype modulates testosterone-dependent activity and reactivity in male mice.

    Broida, J; Svare, B

    1983-03-01

    Adult castration significantly reduced the homecage locomotor activity of both inbred C57BL/6J and DBA/2J and outbred Rockland-Swiss (R-S) male mice. Castrated C57BL animals exhibited greater reductions in this behavior than did the other genotypes. Locomotor activity in a novel environment (reactivity) was also reduced by castration but only for inbred males. In both test situations, postcastration reductions in ambulation were prevented by implants of testosterone (T)-containing Silastic capsules. Thus, testicular hormones promote activity and reactivity in the male mouse in a genotype-dependent fashion.

  18. Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and Female Mice.

    Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A

    2015-07-01

    Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain.

  19. Sim1 Neurons Are Sufficient for MC4R-Mediated Sexual Function in Male Mice.

    Semple, Erin; Hill, Jennifer W

    2018-01-01

    Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown. We hypothesized that single-minded homolog 1 (Sim1) neurons play an important role in the melanocortin-mediated regulation of male sexual behavior. To test this hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1-positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild-type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial amygdala and paraventricular nucleus of the hypothalamus. These mice were paired with sexually experienced females, and their sexual function and behavior was scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed a longer latency to mount, a reduced intromission efficiency, and an inability to reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual deficits seen in tbMC4R null mice. This study implicates melanocortin signaling via the MC4R on Sim1 neurons in the central control of male sexual behavior. Copyright © 2018 Endocrine Society.

  20. Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice

    Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

    2014-01-01

    AIM: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. METHODS...... of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting...... responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar...

  1. Hydrolyzed Casein Reduces Diet-Induced Obesity in Male C57BL/6J Mice

    Lillefosse, Haldis H.; Tastesen, Hanne Sørup; Du, Zhen-Yu

    2013-01-01

    used a factorial ANOVA design to investigate the effects of protein form (intact vs. hydrolyzed casein) and protein level (16 vs. 32 energy percent protein) on body mass gain and adiposity in obesity-prone male C57BL/6J mice fed Western diets with 35 energy percent fat. Mice fed the hydrolyzed casein......The digestion rate of dietary protein is a regulating factor for postprandial metabolism both in humans and animal models. However, few data exist about the habitual consumption of proteins with different digestion rates with regard to the development of body mass and diet-induced obesity. Here, we...... diets had higher spontaneous locomotor activity than mice fed intact casein. During the light phase, mice fed hydrolyzed casein tended (P = 0.08) to have a lower respiratory exchange ratio, indicating lower utilization of carbohydrates as energy substrate relative to those fed intact casein. In further...

  2. Male mice emit distinct ultrasonic vocalizations when the female leaves the social interaction arena

    Mu eYang

    2013-11-01

    Full Text Available Adult male mice emit large number of complex ultrasonic vocalizations (USVs when interacting with adult females. Call numbers and call categories differ greatly among inbred mouse strains. Little is known about USV emissions when the social partner departs. To investigate whether call repertoires and call rates are different when the male is interacting with a female and after the removal of the female, we designed a novel male-female social interaction test in which vocalizations were recorded across three phases. During phase 1, the male subject freely interacts with an unfamiliar estrus female mouse in a clean cage for 5 minutes. During phase 2, the female is removed while the male remains in the cage for 3 minutes. During phase 3, the same female is returned to the cage to rejoin the male subject mouse for 3 minutes. C57BL/6J (B6, FVB.129P2-Pde6b(+ Tyr(c-ch/Ant (FVB, and BTBR T+ tf/J (BTBR male subject mice were tested in this paradigm. All three strains emitted USVs during the absence of the estrous female, although at lower rates. When the female was reintroduced in phase 3, numbers of USVs were similar to the initial introductory phase 1. Strain comparisons indicated fewer calls in pairs of BTBR males and stimulus females than in pairs of B6 males and stimulus females and pairs of FVB males and stimulus females. In the absence of the female, all FVB males vocalized, while only one third of B6 males and one third of BTBR males vocalized. In all three strains, changes in call repertoires were detected after the female was removed. Call categories reverted to the phase 1 pattern when the female was returned in phase 3. Present findings indicate that males of commonly used inbred strains emit USVs when a partner female leaves the testing arena, suggesting that removing a salient social stimulus may be a unique approach to elicit USVs from mice. Our three-phase paradigm may also be useful for studying attention to social cues, and qualitative

  3. Exposure to bifenthrin causes immunotoxicity and oxidative stress in male mice.

    Jin, Yuanxiang; Pan, Xiuhong; Fu, Zhengwei

    2014-09-01

    Bifenthrin (BF) is one of the most commonly used pesticides among the synthetic pyrethroids. The effects of BF exposure on the induction of immunotoxicity and oxidative stress were studied both in adolescent and adult male ICR mice. Both the weights of the spleen and thymus decreased significantly in the adolescent mice when they were treated with 20 mg/kg BF for 3 weeks. We found that the 3-week oral administration of BF during puberty increased the transcriptional levels of the genes TNF and IL2 in the spleen and IL2 as well as IL4 in the thymus. The effect of BF exposure on the induction of oxidative stress was also studied in serum and liver samples. The total antioxidant capacity and activity of superoxide dismutase were altered significantly in the serum of the 20 mg/kg BF-treated adolescent mice, and the activity of glutathione peroxidase (GPX) decreased significantly in the serum of adolescent and adult mice after 3 weeks of oral administration of 20 mg/kg BF. Compared to serum, hepatic GSH content increased significantly in both the adolescent and adult mice exposed to 20 mg/kg BF; hepatic CAT and GPX activities were altered significantly, even in adolescent mice, after treatment with 10 mg/kg BF. Taken together, the results of this study suggest that exposure to BF, especially during puberty, has the potential to induce immunotoxicity accompanied by oxidative stress in male mice. These findings will help in elucidating the mechanism of toxicity induced by BF in mice. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  4. Meiotic chromosomal translocations in male mice induced by X-irradiation

    Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

    1983-01-01

    The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

  5. Induction of dominant lethals in male mice treated as embryos with 35S

    Reddy, K.S.; Reddy, P.P.; Reddy, O.S.

    1980-01-01

    Pregnant female mice were injected (ip) with 20 μCi of 35 S or 0.5 ml of saline (control) on 3.5 day of gestation. The animals were allowed to litter and the (CBA female x C 3 H/He male) F 1 males treated as embryos were tested at maturity (8-10 weeks) for dominant lethal incidence. Each male was mated to 3 untreated virgin females for a period of 3 weeks. The pregnant animals were killed at mid gestation and the uterine contents and corpora lutea were examined. There was a significant increase in the frequency of dominant lethals both at pre- and post-implantation stages in the treated group when compared to controls. As a result a significant increase in dead implantations/female and reduction in live implantations/female were noticed in the treated group. Thus the results clearly delineate the genetic effects of sulfur-35 in mice. (auth.)

  6. Maternal alcohol consumption during pregnancy and semen quality in the male offspring: two decades of follow-up

    Ramlau-Hansen, Cecilia; Toft, G; Jensen, M S

    2010-01-01

    Concurrent alcohol exposure has been associated with reduced fecundity, but no studies have estimated the effect of prenatal alcohol exposure on male fecundity. The aim of this study was to investigate the association between maternal alcohol consumption during pregnancy, semen quality and levels...

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

    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.

  8. Why is young maternal age at first childbirth a risk factor for persistent delinquency in their male offspring? Examining the role of family and parenting factors.

    van Vugt, Eveline; Loeber, Rolf; Pardini, Dustin

    2016-12-01

    Children born to mothers who were younger than average at their first childbirth are at increased risk for future persistent delinquent behaviour, but explanations for this remain unclear. Our aim was to identify possible family and parenting variables that may help explain this relationship. We hypothesised that parental stress, large number of children in the home, low socioeconomic status (including neighbourhood problems) and poor parenting would account for the link between early first motherhood and their offspring's delinquency. Four hundred and sixty-two boys were selected from the Pittsburgh Youth Study, a longitudinal study of a random sample of school boys in Pittsburgh, initially assessed half-yearly and then annually from 7 to 19 years of age, using self-reporting and other reporting methods. Indirect effect models were used to test relationships between variables. Higher levels of parental stress, poorer parent-child communication and caring for a larger number of children all mediated the relationship between maternal youth and persistent delinquency by their boys, but only explained about 20% of it. At least partial explanations of the relationship between a mother's age at first childbirth and persistent delinquency in her male offspring suggest that future research should test whether early interventions with younger mothers to decrease their sense of stress in parenting and improve their capacity for communication with their child(ren) may help to prevent persistent delinquency in their boys. Programmes designed to help young women make more informed and planned decisions about their pregnancies should also be evaluated. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice.

    Takeshita, Hikari; Yamamoto, Koichi; Nozato, Satoko; Inagaki, Tadakatsu; Tsuchimochi, Hirotsugu; Shirai, Mikiyasu; Yamamoto, Ryohei; Imaizumi, Yuki; Hongyo, Kazuhiro; Yokoyama, Serina; Takeda, Masao; Oguro, Ryosuke; Takami, Yoichi; Itoh, Norihisa; Takeya, Yasushi; Sugimoto, Ken; Fukada, So-Ichiro; Rakugi, Hiromi

    2017-02-08

    The conventional forelimb grip strength test is a widely used method to assess skeletal muscle function in rodents; in this study, we modified this method to improve its variability and consistency. The modified test had lower variability among trials and days than the conventional test in young C57BL6 mice, especially by improving the variabilities in male. The modified test was more sensitive than the conventional test to detect a difference in motor function between female and male mice, or between young and old male mice. When the modified test was performed on male mice during the aging process, reduction of grip strength manifested between 18 and 24 months of age at the group level and at the individual level. The modified test was similar to the conventional test in detecting skeletal muscle dysfunction in young male dystrophic mice. Thus, the modified forelimb grip strength test, with its improved validity and reliability may be an ideal substitute for the conventional method.

  10. Papain-induced experimental pulmonary emphysema in male and female mice.

    Machado, Mariana Nascimento; Figueirôa, Silviane Fernandes da Silva; Mazzoli-Rocha, Flavia; Valença, Samuel dos Santos; Zin, Walter Araújo

    2014-08-15

    In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Effect of Variable Doses of Zinc Oxide Nanoparticles on Male Albino Mice Behavior.

    Zahra, Javeria; Iqbal, Shahid; Zahra, Kiran; Javed, Zulha; Shad, Muhammad Aslam; Akbar, Atif; Ashiq, Muhammad Naeem; Iqbal, Furhan

    2017-02-01

    Zinc oxide nanoparticles (ZnO NPs) have diverse utility these days ranging from being part of nanosensors to be ingredient of cosmetics. Present study was designed to report the effect of variable doses of ZnO NPs on selected aspects of male albino mice behavior. Nano particles were synthesized by sol-gel auto-combustion method (Data not shown here). 10 week old male albino mice were divided into four experimental groups; group A, B and C were orally supplemented with 50 (low dose), 300 (medium dose) and 600 mg/ml solvent/kg body weight (high dose) of ZnO NPs for 4 days. Group D (control) orally received 0.2 M sodium phosphate buffer (solvent for ZnO NPs) for the same duration. A series of neurological tests (Rota rod, open field, novel object and light-dark box test) were conducted in all groups and performance was compared between ZnO NPs treated and control group. Muscular functioning during rota rod test was significantly improved in all ZnO NPs treated mice as compared to control group. While no significant differences in open field, novel object and light-dark box test performance were observed when data from studied parameters of specific ZnO NPs treatment were compared with the control group indicating that applied doses of ZnO NPs did not affect the exploratory, anxiolytic behavior and object recognition capability of adult male albino mice.

  12. Efficacy of protocols for induction of chronic hyperthyroidism in male and female mice.

    Engels, Kathrin; Rakov, Helena; Zwanziger, Denise; Hönes, Georg Sebastian; Rehders, Maren; Brix, Klaudia; Köhrle, Josef; Möller, Lars Christian; Führer, Dagmar

    2016-10-01

    Protocols for induction of hyperthyroidism in mice are highly variable and mostly involve short-term thyroid hormone (TH) treatment. In addition, little is known about a possible influence of sex on experimental TH manipulation. Here we analyzed the efficacy of intraperitoneal vs. oral levothyroxine (T4) administration to induce chronic hyperthyroidism in male and female mice and asked which T4 dosing intervals are required to achieve stable organ thyrotoxicosis. T4 was administered intraperitoneally or orally over a period of 6/7 weeks. Assessment included monitoring of body weight, TH serum concentrations, and serial quantitative TH target gene expression analysis in liver and heart. Our results show that both intraperitoneal and oral T4 treatment are reliable methods for induction of chronic hyperthyroidism in mice. Thereby T4 injection intervals should not exceed 48 h and oral levothyroxine should be administered continuously during experiments and up to sacrifice to ensure a hyperthyroid organ state. Furthermore, we found a sex-dependent variation in levothyroxine-induced TH serum state, with significantly higher T4 concentrations in female mice, while expression of investigated classical TH responsive genes in liver and heart did not vary with animal's sex. In summary, our study shows that common approaches for rendering rodents thyrotoxic can also be used for induction of chronic hyperthyroidism in male and female mice. Thereby T4 dosing intervals are critical as are read-out parameters to verify a chronic thyrotoxic organ state.

  13. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Maternal modulation of paternal effects on offspring development.

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

    2018-03-14

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

  15. Repeated in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure affects male gonads in offspring, leading to sex ratio changes in F2 progeny

    Ikeda, Masahiko; Tamura, Masashi; Yamashita, Junko; Suzuki, Chinatsu; Tomita, Takako

    2005-01-01

    The effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male rat offspring (F 1 ) and the sex ratio of the subsequent generation (F 2 ) were examined. Female Holtzman rats were gavaged with an initial loading dose of 400 ng/kg TCDD prior to mating, followed by weekly maintenance doses of 80 ng/kg during mating, pregnancy, and the lactation period. Maternal exposure to TCDD had no significant effects on fetus/pup (F 1 ) mortality, litter size, or sex ratio on gestation day (GD) 20 or postnatal day (PND) 2. The TCDD concentration in maternal livers and adipose tissue on GD20 was 1.21 and 1.81 ng/kg, respectively, and decreased at weaning to 0.72 in the liver and 0.84 in the adipose tissue. In contrast, the TCDD concentration in pup livers was 1.32 ng/kg on PND2 and increased to 1.80 ng/kg at weaning. Ventral prostate weight of male offspring was significantly decreased by TCDD exposure on PND28 and 120 compared with that of controls. Weight of the testes, cauda epididymides, and seminal vesicle, and sperm number in the cauda epididymis were not changed by TCDD exposure at PND120. TCDD- or vehicle-exposed male offspring were mated with unexposed females. The sex ratio (percentage of male pups) of F 2 offspring was significantly reduced in the TCDD-exposed group compared with controls. These results suggest that in utero and lactational TCDD exposures affect the development of male gonads in offspring (F 1 ), leading to changes in the sex ratio of the subsequent generation (F 2 )

  16. Analysis of chromosome rearrangements on the basis of synaptonemal complexes in the offspring of mice exposed to γ-rays

    Kalikinskaya, E.I.; Bogdanov, Yu.F.; Kolomiets, O.L.; Shevchenko, V.A.

    1986-01-01

    Electron-microscopic analysis of synaptonemic complexes (SC), spread on the hypophase surface, was conducted to investigate chromosome rearrangements in sterile and semisterile F 1 malemause offsprings, exposed to 5 Gy γ-rays Paralelly Chromosome rearrangement account in diakinesis-metaphase 1 was conducted using light microscope, in the same animals. During SC analysis in pachytene chromosome rearrangements were found in 63% of spermatocytes. Under chromosome analysis in diakinesis-metaphase 1 in the same animals chromosome rearrangements were found only in 32% of cells. SC analysis allows one to reveal chromosome rearrangements, which can not be revealed in diakinesis-metaphase 1

  17. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until d...

  18. Nucleus Accumbens Dopamine Signaling Regulates Sexual Preference for Females in Male Mice.

    Beny-Shefer, Yamit; Zilkha, Noga; Lavi-Avnon, Yael; Bezalel, Nadav; Rogachev, Ilana; Brandis, Alexander; Dayan, Molly; Kimchi, Tali

    2017-12-12

    Sexual preference for the opposite sex is a fundamental behavior underlying reproductive success, but the neural mechanisms remain unclear. Here, we examined the role of dopamine signaling in the nucleus accumbens core (NAcc) in governing chemosensory-mediated preference for females in TrpC2 -/- and wild-type male mice. TrpC2 -/- males, deficient in VNO-mediated signaling, do not display mating or olfactory preference toward females. We found that, during social interaction with females, TrpC2 -/- males do not show increased NAcc dopamine levels, observed in wild-type males. Optogenetic stimulation of VTA-NAcc dopaminergic neurons in TrpC2 -/- males during exposure to a female promoted preference response to female pheromones and elevated copulatory behavior toward females. Additionally, we found that signaling through the D1 receptor in the NAcc is necessary for the olfactory preference for female-soiled bedding. Our study establishes a critical role for the mesolimbic dopaminergic system in governing pheromone-mediated responses and mate choice in male mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Nucleus Accumbens Dopamine Signaling Regulates Sexual Preference for Females in Male Mice

    Yamit Beny-Shefer

    2017-12-01

    Full Text Available Sexual preference for the opposite sex is a fundamental behavior underlying reproductive success, but the neural mechanisms remain unclear. Here, we examined the role of dopamine signaling in the nucleus accumbens core (NAcc in governing chemosensory-mediated preference for females in TrpC2−/− and wild-type male mice. TrpC2−/− males, deficient in VNO-mediated signaling, do not display mating or olfactory preference toward females. We found that, during social interaction with females, TrpC2−/− males do not show increased NAcc dopamine levels, observed in wild-type males. Optogenetic stimulation of VTA-NAcc dopaminergic neurons in TrpC2−/− males during exposure to a female promoted preference response to female pheromones and elevated copulatory behavior toward females. Additionally, we found that signaling through the D1 receptor in the NAcc is necessary for the olfactory preference for female-soiled bedding. Our study establishes a critical role for the mesolimbic dopaminergic system in governing pheromone-mediated responses and mate choice in male mice.

  20. MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

    Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

    2015-08-06

    Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory

  1. Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

    Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

    2010-11-01

    Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment.

  2. Identification of SOX3 as an XX male sex reversal gene in mice and humans.

    Sutton, Edwina; Hughes, James; White, Stefan; Sekido, Ryohei; Tan, Jacqueline; Arboleda, Valerie; Rogers, Nicholas; Knower, Kevin; Rowley, Lynn; Eyre, Helen; Rizzoti, Karine; McAninch, Dale; Goncalves, Joao; Slee, Jennie; Turbitt, Erin; Bruno, Damien; Bengtsson, Henrik; Harley, Vincent; Vilain, Eric; Sinclair, Andrew; Lovell-Badge, Robin; Thomas, Paul

    2011-01-01

    Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome-linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box-containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad.

  3. Identification of SOX3 as an XX male sex reversal gene in mice and humans

    Sutton, Edwina; Hughes, James; White, Stefan; Sekido, Ryohei; Tan, Jacqueline; Arboleda, Valerie; Rogers, Nicholas; Knower, Kevin; Rowley, Lynn; Eyre, Helen; Rizzoti, Karine; McAninch, Dale; Goncalves, Joao; Slee, Jennie; Turbitt, Erin; Bruno, Damien; Bengtsson, Henrik; Harley, Vincent; Vilain, Eric; Sinclair, Andrew; Lovell-Badge, Robin; Thomas, Paul

    2010-01-01

    Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome–linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box–containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad. PMID:21183788

  4. Expression of group III metabotropic glutamate receptors in the reproductive system of male mice.

    Marciniak, Marcin; Chruścicka, Barbara; Lech, Tomasz; Burnat, Grzegorz; Pilc, Andrzej

    2016-03-01

    Although the presence of metabotropic glutamate (mGlu) receptors in the central nervous system is well documented, they have recently been found in peripheral and non-neuronal tissues. In the present study we investigated the expression of group III mGlu receptors in the reproductive system of male mice. Reverse transcription-polymerase chain reaction analysis revealed the presence of mGlu6, mGlu7 and mGlu8 (but not mGlu4) receptor transcripts in testes and epididymides from adult mice. In addition, expression of mGlu6 (Grm6) and mGlu8 receptor (Grm8) mRNA was detected in spermatozoa isolated from the vas deferens. The vas deferens was found to contain only mGlu7 receptor (Grm7) mRNA, which was particularly intense in 21-day-old male mice. In penile homogenates, only the mGlu7 receptor signal was detected. Genetic ablation of the mGlu7 receptor in males led to fertility disorders manifested by decreased insemination capability as well as deterioration of sperm parameters, particularly sperm motility, vitality, sperm membrane integrity and morphology, with a simultaneous increase in sperm concentration. These results indicate that constitutively expressed mGlu receptors in the male reproductive system may play an important role in ejaculation and/or erection processes, as well as in the formation and maturation of spermatozoa.

  5. Growth and development of male "little" mice assessed with Parks' theory of feeding and growth.

    Puche, Rodolfo C; Alloatti, Rosa; Chapo, Gustavo

    2002-01-01

    This work was designed to characterize the appetite kinetics and growth of male C57BL/6J (lit) mice. Those variables were assessed with Parks' function of ad libitum feeding and growth. Heterozygous mice (lit/+) attained their mature weight at 12-15 weeks of age, peak growth rate (3.5 g/week) at 5 weeks and displayed the normal decay of food conversion efficiency as a function of age. The homozygous genotype has a chronic defect in the synthesis and secretion of growth hormone (GH). Homozygous mice could not be assessed with Park's function. From the 4th to the 15th week of age, body weight increased linearly and exhibited constant food conversion efficiency. Food intake of both genotypes was commensurate with their body weights. Lit/lit mice became progressively obese. At 40 weeks of age, body fat of lit/lit mice was fivefold that of lit/+ and their body weight was similar to their heterozygous controls. The chronic deficiency of growth hormone produced a lower bone mass (compared to heterozygous controls). Bone mass of both genotypes attained maturity at 12-15 weeks with a maximum growth rate at 5 weeks. Body weight and bone mass grow harmoniously in lit/+ but not in lit/lit mice.

  6. The contribution of the Y chromosome to hybrid male sterility in house mice.

    Campbell, Polly; Good, Jeffrey M; Dean, Matthew D; Tucker, Priscilla K; Nachman, Michael W

    2012-08-01

    Hybrid sterility in the heterogametic sex is a common feature of speciation in animals. In house mice, the contribution of the Mus musculus musculus X chromosome to hybrid male sterility is large. It is not known, however, whether F1 male sterility is caused by X-Y or X-autosome incompatibilities or a combination of both. We investigated the contribution of the M. musculus domesticus Y chromosome to hybrid male sterility in a cross between wild-derived strains in which males with a M. m. musculus X chromosome and M. m. domesticus Y chromosome are partially sterile, while males from the reciprocal cross are reproductively normal. We used eight X introgression lines to combine different X chromosome genotypes with different Y chromosomes on an F1 autosomal background, and we measured a suite of male reproductive traits. Reproductive deficits were observed in most F1 males, regardless of Y chromosome genotype. Nonetheless, we found evidence for a negative interaction between the M. m. domesticus Y and an interval on the M. m. musculus X that resulted in abnormal sperm morphology. Therefore, although F1 male sterility appears to be caused mainly by X-autosome incompatibilities, X-Y incompatibilities contribute to some aspects of sterility.

  7. Below background levels of blood lead impact cytokine levels in male and female mice

    Iavicoli, I.; Carelli, G.; Stanek, E.J.; Castellino, N.; Calabrese, E.J.

    2006-01-01

    A number of studies have documented that Pb exerts immunotoxic effects on T lymphocytes. In studies designed to explore this general response over a broad dose range, female Swiss mice were administered six different diets containing Pb acetate 1 day after mating. During lactation, the mothers received the same feed given during pregnancy, and the same diets were administered to the offspring for 9 months after weaning. At the end of exposure, blood Pb level in the offspring was determined, and possible changes in two type 1 cytokines (IL-2, INF-γ) and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb levels (40 and 400 ppm), a significant increase in IL-4 production was associated with a profound decrease in INF-γ and IL-2 production. At the lowest Pb diet level (0.02 ppm), which resulted in a blood lead level of (0.8 μg/dL), which is below background (2-3 μg/dL) values in humans, increases in INF-γ and IL-2 production along with a significant decrease in IL-4 production were observed. The findings provide evidence of a reversal of lead-induced cytokine skewing depending on the blood lead concentration. As blood lead concentration increases, there is a notable skewing toward Th2, while the pattern is reversed favoring Th1 development at lower blood lead values. The present findings are also notable since they indicate the potential for dietary Pb to have significant biological effects below normal background concentrations

  8. No evidence for female discrimination against male house mice carrying a selfish genetic element.

    Sutter, Andreas; Lindholm, Anna K

    2016-12-01

    Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous (+/ t ) mice leads to high embryo mortality. Previous experiments showing that +/ t females avoid this incompatibility cost by preferring +/+ versus +/ t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against +/ t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between gametes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by +/ t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.

  9. Dual role of betel leaf extract on thyroid function in male mice.

    Panda, S; Kar, A

    1998-12-01

    The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed.

  10. Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice.

    Zang, Zhi-Jun; Tang, Hong-Feng; Tuo, Ying; Xing, Wei-Jie; Ji, Su-Yun; Gao, Yong; Deng, Chun-Hua

    2016-01-01

    Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo.

  11. 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.

    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.

  12. Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

    Hai, Lan; Hiremath, Deepak S; Paquet, Marilène; Narayan, Prema

    2017-05-01

    The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

  13. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    Martinić, Roko; Šošić, Hrvoje; Turčić, Petra; Konjevoda, Paško; Fučić, Aleksandra; Stojković, Ranko; Aralica, Gorana; Gabričević, Mario; Weitner, Tin; Štambuk, Nikola

    2014-01-01

    Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for se...

  14. Effects of fetal exposure to gamma rays on aggressive behavior in adult male mice

    Minamisawa, Takeru; Hirokaga, Kouichi; Sasaki, Shunsaku; Noda, Yutaka.

    1992-01-01

    Aggressive behavior (AB) in first generation (F 1 ) hybrid male C57BL/6 x C3H mice irradiated on the 14th day of gestation was studied at 100-135 days of age. Gravid female mice were irradiated with 1.0 or 2.0 Gy of gamma rays to the whole body. The AB of pairs of mice were recorded with a capacitance-induction motility monitor and on videotape. Recordings were continued for 90 min, starting at 2:00 PM. Vigorous wrestling, boxing and biting were regarded as AB. Data recorded at 15-min intervals were stored on micro-computer discs. The body weight for the irradiated group was significantly lower than that for the control group. The number of instances of AB was significantly higher in the irradiated group. The AB of the 2.0 Gy group was significantly more intensive than that of the control group. No difference in the duration of AB was found for the 2 irradiated and the control groups. Results demonstrate that male mice irradiated prenatally show increased aggressiveness. (author)

  15. Cis-bifenthrin induces immunotoxicity in adolescent male C57BL/6 mice.

    Wang, Xia; Gao, Xingli; He, Bingnan; Zhu, Jiawei; Lou, Huihui; Hu, Qinglian; Jin, Yuanxiang; Fu, Zhengwei

    2017-07-01

    Bifenthrin (BF) is an important synthetic pyrethroid. Previous studies have demonstrated that cis-BF exhibits toxic effects on development, the neurological, reproductive and endocrine system. In this study, we evaluated the immunotoxicity caused by cis-BF in adolescent male C57BL/6 mice. Mice were exposed orally to 0, 5, 10, and 20 mg/kg/d for 3 weeks. The results showed that body weight, spleen weight, and splenic cellularity decreased in mice exposed to 20 mg/kg/d cis-BF. Additionally, we found that the mRNA levels of the pro-inflammatory factors IL-1β, IL-6, CXCL-1, and TNF-α, in peritoneal macrophages, the spleen, and the thymus were inhibited in the cis-BF-treated groups. Moreover, MTT assays demonstrated that cis-BF inhibited splenocyte proliferation stimulated by LPS or Con A, as well as the secretion of IFN-γ on Con A stimulation. Collectively, the results of this study suggest that exposure to cis-BF has the potential to induce immunotoxicity in adolescent male C57BL/6 mice. © 2017 Wiley Periodicals, Inc.

  16. Silk amino acids improve physical stamina and male reproductive function of mice.

    Shin, Sunhee; Yeon, Seongho; Park, Dongsun; Oh, Jiyoung; Kang, Hyomin; Kim, Sunghyun; Joo, Seong Soo; Lim, Woo-Taek; Lee, Jeong-Yong; Choi, Kyung-Chul; Kim, Ki Yon; Kim, Seung Up; Kim, Jong-Choon; Kim, Yun-Bae

    2010-01-01

    The effects of a silk amino acid (SAA) preparation on the physical stamina and male reproductive function of mice were investigated. Eight-week-old male ICR mice (29-31 g) were orally administered SAA (50, 160 or 500 mg/kg) for 44 d during 30-min daily swimming exercise. The mice were subjected to a weight-loaded (5% of body weight) forced swimming on the 14th, 28th and 42nd day to determine maximum swimming time, and after a 2-d recovery period (treated with SAA without swimming exercise), parameters related to fatigue and reproductive function were analyzed from blood, muscles and reproductive organs. Repeated swimming exercise increased the maximum swimming time to some extent, in spite of a marked reduction in body weight gain, and SAA further enhanced the stamina in a dose-dependent manner. Forced swimming exercises increased blood parameters of tissue injury, but depleted blood glucose and tissue glycogen, which were substantially prevented by SAA treatment. In addition, SAA significantly reduced the muscular thiobarbituric acid-reactive substances and blood corticosterone content increased by forced swimming. Swimming exercise decreased the blood testosterone level, which was recovered by SAA, leading to enhanced sperm counts. These combined results indicate that SAA not only enhances physical stamina by minimizing damage to tissues, including muscles, as well as preventing energy depletion caused by swimming stress, but also improves male reproductive function by increasing testosterone and sperm counts.

  17. Genetic and hormonal control of hepatic steatosis in female and male mice.

    Norheim, Frode; Hui, Simon T; Kulahcioglu, Emre; Mehrabian, Margarete; Cantor, Rita M; Pan, Calvin; Parks, Brian W; Lusis, Aldons J

    2017-01-01

    The etiology of nonalcoholic fatty liver disease is complex and influenced by factors such as obesity, insulin resistance, hyperlipidemia, and sex. We now report a study on sex difference in hepatic steatosis in the context of genetic variation using a population of inbred strains of mice. While male mice generally exhibited higher concentration of hepatic TG levels on a high-fat high-sucrose diet, sex differences showed extensive interaction with genetic variation. Differences in percentage body fat were the best predictor of hepatic steatosis among the strains and explained about 30% of the variation in both sexes. The difference in percent gonadal fat and HDL explained 9.6% and 6.7% of the difference in hepatic TGs between the sexes, respectively. Genome-wide association mapping of hepatic TG revealed some striking differences in genetic control of hepatic steatosis between females and males. Gonadectomy increased the hepatic TG to body fat percentage ratio among male, but not female, mice. Our data suggest that the difference between the sexes in hepatic TG can be partly explained by differences in body fat distribution, plasma HDL, and genetic regulation. Future studies are required to understand the molecular interactions between sex, genetics, and the environment. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  18. Focal lesions within the ventral striato-pallidum abolish attraction for male chemosignals in female mice.

    Agustín-Pavón, Carmen; Martínez-García, Fernando; Lanuza, Enrique

    2014-02-01

    In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this region, but not of regions in the posterolateral striato-pallidum, abolish the attraction of female mice for male chemosignals, without affecting significantly their preference for a different natural reward (a sucrose solution). These results show that, at least in female mice, the integrity of the anterior aspect of the medioventral striato-pallidum, comprising a portion of the olfactory tubercle and associated islands of Calleja, is necessary for the attraction for male chemosignals. We suggest that this region contributes to the processing of the hedonic properties of biologically significant odorants. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Both paternal exercise and healthy diet are required to protect offspring from high fat diet-induced obesity and type 2 diabetes risk in mice

    Objective: Paternal eating and physical activity behaviors peri-conception may influence offspring obesity and type 2 diabetes (T2D) risk. A recent study showed that paternal exercise increased offspring susceptibility to obesity when the offspring consumed a high fat (HF) diet. However, it is not y...

  20. Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: Effects on liver DNA strand breaks in dams and offspring

    Jackson, Petra; Hougaard, Karin Sørig; Boisen, Anne Mette Zenner

    2011-01-01

    cells and liver, and in offspring liver. Persistent lung inflammation was observed in exposed mothers. Inhalation exposure induced more DNA strand breaks in the liver of mothers and their offspring, whereas intratracheal instillation did not. Neither inhalation nor instillation affected gestation...... and lactation. Maternal inhalation exposure to Printex 90-induced liver DNA damage in the mothers and the in utero exposed offspring....

  1. Study on The Reproductive Organs and Fertility of The Male Mice following Administration of Metronidazole

    Poonam Singh

    2013-01-01

    Full Text Available Background: Metronidazole (MTZ is commonly used as an antibacterial and antiprotozoaldrug. Various doses of MTZ have been reported to inhibit spermatogenic activityand sperm indices.Materials and Methods: In this experimental study, dose-dependent effects of MTZ onthe structural and functional integrity of the testis and accessory reproductive organshave been investigated. Adult male mice of Swiss strain were administered orally withMTZ at the doses of 250 mg/kgBW/day and 500 mg/kgBW/day for 28 consecutive daysto study the changes in the testis, epididymis, seminal vesicle, sperm indices and fertility.Reversal effects of the drug were also studied on the same mice, 42 days after cessationof the treatment.Results: Therapeutic dose of MTZ (250 mg/kgBW/day neither altered the weights ofthe testis, epididymis and seminal vesicle nor their histoarchitecture and sperm indices.The drug at the high dose (500 mg/kg BW/day caused significant reductions in theweights of the testis and epididymis. Histoarchitecture of the testis and epididymis at thehigh dose revealed marked regressive changes while that of seminal vesicle remainedunaffected. Significant reductions were noticed in the motility, viability and count ofepididymal spermatozoa while the concentrations of epididymal sialic acid and seminalvesicular fructose remained unaltered after the treatment. No significant changes werenoticed in the mating ability as well as in the level of serum testosterone in the treatedmice. Fertility of the male mice treated with high dose of MTZ declined markedly leadingto an increase in pre- and postimplantation loss while a significant decrease wasnoticed in the number of live blastocysts in females impregnated with such males. MTZinducedchanges in the male reproductive organs and fertility were reinstated 42 daysafter cessation of the treatment.Conclusion: High dose of MTZ induced reversible deleterious effects on the male reproductionand fertility.

  2. Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

    Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

    2018-06-08

    Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

  3. An Essential Physiological Role for MCT8 in Bone in Male Mice.

    Leitch, Victoria D; Di Cosmo, Caterina; Liao, Xiao-Hui; O'Boy, Sam; Galliford, Thomas M; Evans, Holly; Croucher, Peter I; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E; Refetoff, Samuel; Williams, Graham R; Bassett, J H Duncan

    2017-09-01

    T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance.

  4. Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

    Isabella M. Fuentes

    2016-12-01

    Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

  5. Skeletal response of male mice to anabolic hormone therapy in the absence of the Igfals gene.

    Kennedy, Oran D; Sun, Hui; Wu, Yingjie; Courtland, Hayden-William; Williams, Garry A; Cardoso, Luis; Basta-Pljakic, Jelena; Schaffler, Mitchell B; Yakar, Shoshana

    2014-03-01

    IGF-I is a critical regulator of skeletal acquisition, which acts in endocrine and autocrine/paracrine modes. In serum, IGF-I is carried by the IGF-binding proteins in binary complexes. Further stabilization of these complexes is achieved by binding to the acid labile subunit (ALS) in a ternary complex (of IGF-I-IGF-binding protein 3/5-ALS). Ablation of the Igfals gene in humans (ALS deficiency) and mice (ALS knockout [ALSKO]) leads to markedly decreased serum IGF-I levels, growth retardation, and impaired skeletal acquisition. To investigate whether hormonal replacement therapy would improve the skeletal phenotype in cases of Igfals gene ablation, we treated male ALSKO mice with GH, IGF-I, or a combination of both. Treatments were administered to animals between 4 and 16 weeks of age or from 8 to 16 weeks of age. Although all treatment groups showed an increase (20%) in serum IGF-I levels, there was no increase in body weight, weight gain, or bone length in either age group. Despite the blunted linear growth in response to hormone therapy, ALSKO mice treated with GH showed radial bone growth, which contributed to bone strength tested by 4-point bending. We found that ALSKO mice treated with GH showed increased total cross-sectional area, cortical bone area, and cortical thickness by microtomography. Dynamic histomorphometry showed that although GH and double treatment groups resulted in trends towards increased bone formation parameters, these did not reach significance. However, bone resorption parameters were significantly increased in all treatment groups. ALSKO mice treated between 4 and 16 weeks of age showed minor differences in bone traits compared with vehicle-treated mice. In conclusion, treatment with GH and IGF-I do not work synergistically to rescue the stunted growth found in mice lacking the Igfals gene. Although GH alone appears to increase bone parameters slightly, it does not affect body weight or linear growth.

  6. 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.

    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.

  7. 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

    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.

  8. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence.

    Yui K Matsumoto

    Full Text Available Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male-female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study.

  9. Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice.

    Good, Jeffrey M; Handel, Mary Ann; Nachman, Michael W

    2008-01-01

    House mice offer a powerful system for dissecting the genetic basis of phenotypes that isolate species in the early stages of speciation. We used a series of reciprocal crosses between wild-derived strains of Mus musculus and M. domesticus to examine F(1) hybrid male sterility, one of the primary phenotypes thought to isolate these species. We report four main results. First, we found significantly smaller testes and fewer sperm in hybrid male progeny of most crosses. Second, in some crosses hybrid male sterility was asymmetric and depended on the species origin of the X chromosome. These observations confirm and extend previous findings, underscoring the central role that the M. musculus X chromosome plays in reproductive isolation. Third, comparisons among reciprocal crosses revealed polymorphism at one or more hybrid incompatibilities within M. musculus. Fourth, the spermatogenic phenotype of this polymorphic interaction appears distinct from previously described hybrid incompatibilities between these species. These data build on previous studies of speciation in house mice and show that the genetic basis of hybrid male sterility is fairly complex, even at this early stage of divergence.

  10. Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

    Waalkes, Michael P.; Liu Jie; Ward, Jerrold M.; Diwan, Bhalchandra A.

    2006-01-01

    Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 μg/pup/day) or tamoxifen (TAM; 10 μg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-α, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES

  11. Incorporation and metabolism of tritium in pregnant mice and their offspring after feeding organically labelled tritiated milk powder during pregnancy

    Bruwaene, R. van; Gerber, G.B.; Kirchmann, R.; Maes, J.; Fagniart, E.

    1982-01-01

    Food mixed from equal amounts of organically labelled tritiated milk powder and normal food pellets was given to mice during pregnancy and lactation. At birth, some new-born were swapped with those from non-exposed mothers to compare separately accumulation and metabolism during pregnancy and lactation. Young mice were sacrificed at different time after birth, and tritium activity in different organs was determined. Tritium activity was also determined in maternal organs at various times during and after the 42 days feeding period. The activity per g in some tissues of the young, particularly in fat, exceeded that of the food given, probably as a result of the high activity and low metabolic dilution of the fats in the food. Young mice contaminated during lactation and pregnancy contained still detectible activity at an age of 2 months. Activity was nearly the same in mice receiving tritium only during lactation as in those receiving it also during pregnancy. Dilution was more marked due to rapid growth when tritium application was discontinued at birth. Tritium water was replaced most rapidly, organic tritium in brain turned over most slowly with and additional metabolic component of a half life in the order of 1 month. Organic tritium in liver displayed an intermediate half life. (author)

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

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

    2015-05-08

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

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

    Matthew P.G. Barnett

    2015-05-01

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

  14. Animal models of physiologic markers of male reproduction: genetically defined infertile mice

    Chubb, C.

    1987-10-01

    The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of the investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, the authors investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. They propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.

  15. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  16. Relationships among estrogen receptor, oxytocin and vasopressin gene expression and social interaction in male mice.

    Murakami, G; Hunter, R G; Fontaine, C; Ribeiro, A; Pfaff, D

    2011-08-01

    The incidence of social disorders such as autism and schizophrenia is significantly higher in males, and the presentation more severe, than in females. This suggests the possible contribution of sex hormones to the development of these psychiatric disorders. There is also evidence that these disorders are highly heritable. To contribute toward our understanding of the mechanisms underlying social behaviors, particularly social interaction, we assessed the relationship of social interaction with gene expression for two neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), using adult male mice. Social interaction was positively correlated with: oxytocin receptor (OTR) and vasopressin receptor (V1aR) mRNA expression in the medial amygdala; and OT and AVP mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). When mice representing extremes of social interaction were compared, all of these mRNAs were more highly expressed in high social interaction mice than in low social interaction mice. OTR and V1aR mRNAs were highly correlated with estrogen receptor α (ERα) mRNA in the medial amygdala, and OT and AVP mRNAs with estrogen receptor β (ERβ) mRNA in the PVN, indicating that OT and AVP systems are tightly regulated by estrogen receptors. A significant difference in the level of ERα mRNA in the medial amygdala between high and low social interaction mice was also observed. These results support the hypothesis that variations of estrogen receptor levels are associated with differences in social interaction through the OT and AVP systems, by upregulating gene expression for those peptides and their receptors. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. GPR56 is essential for testis development and male fertility in mice.

    Chen, Guangchun; Yang, Liquan; Begum, Shahinoor; Xu, Lei

    2010-12-01

    Testis development is critical for male fertility and continuation of the mammalian species. Essential structural components of testes are seminiferous tubules, which are lined by Sertoli cells and provide nutrients and physical protection for the maturation of sperm. Seminiferous tubule formation is initiated in embryos as testis cords and relies on their remodeling for maturation during development. Recently, three-dimensional image analyses showed that testis cords in different parts of embryonic gonads undergo distinct remodeling processes. How this asymmetric remodeling is regulated has not been investigated. We report here that the absence of an adhesion G protein-coupled receptor, GPR56, leads to partial disruption of seminiferous tubules and reduced fertility in male mice. The defects appear to originate asymmetrically in embryonic gonads, but subsequent to the initial establishment of testis cords, suggesting that GPR56 might act to establish a spatial and/or temporal cue for asymmetric cord remodeling during male gonad development. © 2010 Wiley-Liss, Inc.

  18. Differences in peripheral sensory input to the olfactory bulb between male and female mice

    Kass, Marley D.; Czarnecki, Lindsey A.; Moberly, Andrew H.; McGann, John P.

    2017-04-01

    Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

  19. Differential neurotoxic effects of in utero and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice.

    Haijima, Asahi; Lesmana, Ronny; Shimokawa, Noriaki; Amano, Izuki; Takatsuru, Yusuke; Koibuchi, Noriyuki

    2017-01-01

    We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development.

  20. Male fertility is reduced by chronic intermittent hypoxia mimicking sleep apnea in mice.

    Torres, Marta; Laguna-Barraza, Ricardo; Dalmases, Mireia; Calle, Alexandra; Pericuesta, Eva; Montserrat, Josep M; Navajas, Daniel; Gutierrez-Adan, Alfonso; Farré, Ramon

    2014-11-01

    Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and oxidative stress. However, it is unknown whether intermittent hypoxia mimicking OSA modifies male fertility. We tested the hypothesis that male fertility is reduced by chronic intermittent hypoxia mimicking OSA in a mouse model. Case-control comparison in a murine model. University research laboratory. Eighteen F1 (C57BL/6xCBA) male mice. Mice were subjected to a pattern of periodic hypoxia (20 sec at 5% O2 followed by 40 sec of room air) 6 h/day for 60 days or normoxia. After this period, mice performed a mating trial to determine effective fertility by assessing the number of pregnant females and fetuses. After euthanasia, oxidative stress in testes was assessed by measuring the expression of glutathione peroxidase 1 (Gpx1) and superoxide dismutase-1 (Sod1) by reverse-transcription polymerase chain reaction. Sperm motility was determined by Integrated Semen Analysis System (ISAS). Intermittent hypoxia significantly increased testicular oxidative stress, showing a reduction in the expression of Gpx1 and Sod1 by 38.9% and 34.4%, respectively, as compared with normoxia (P intermittent hypoxia group (P = 0.04). The proportion of pregnant females and number of fetuses per mating was significantly lower in the intermittent hypoxia group (0.33 ± 0.10 and 2.45 ± 0.73, respectively) than in normoxic controls (0.72 ± 0.16 and 5.80 ± 1.24, respectively). These results suggest that the intermittent hypoxia associated with obstructive sleep apnea (OSA) could induce fertility reduction in male patients with this sleep breathing disorder.

  1. Early social enrichment provided by communal nest increases resilience to depression-like behavior more in female than in male mice.

    D'Andrea, Ivana; Gracci, Fiorenza; Alleva, Enrico; Branchi, Igor

    2010-12-20

    Early experiences produce persistent changes in behavior and brain function. Being reared in a communal nest (CN), consisting of a single nest where three mouse mothers keep their pups together and share care-giving behavior from birth to weaning, provides an highly stimulating social environment to the developing pup since both mother-offspring and peer-to-peer interactions are markedly increased. Here we show that being reared in a CN affects adult behavior of CD-1 mice in a gender-dependent fashion, with reduced depression-like responses in females and increased anxiety-like behavior in males. In particular, CN females showed higher sucrose preference at baseline condition, drinking more sweet solution compared to female mice reared in a standard laboratory condition (SN). In the isolation test, both SN and CN females showed a reduction in sucrose preference after exposure to isolation stress. However, after 24h, only CN females significantly recovered. Finally, in the forced swim test, compared to SN, CN females spent longer time floating, a behavioral response that in the CN model has been inversely associated with display of endophenotypes of depression. With regard to the emotional response, CN males displayed an increased anxiety-like behavior in comparison to SN, spending less time in the open arms and displaying reduced head-dippings in the elevated plus-maze test. No difference was found in females. Overall, our findings show that gender and early experiences interact in modulating adult behavior. In particular, we show that early experiences modified developmental trajectories shaping adult endophenotypes of depression more markedly in females than in males. Copyright 2010 Elsevier B.V. All rights reserved.

  2. Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

    Lim, S V; Marenzana, M; Hopkinson, M; List, E O; Kopchick, J J; Pereira, M; Javaheri, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2015-04-01

    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites.

  3. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology. © 2015 Wiley Periodicals, Inc.

  4. Influence of chronic exposure to uranium on male reproduction in mice

    Llobet, J.M.; Sirvent, J.J.; Ortega, A.; Domingo, J.L.

    1991-01-01

    Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day

  5. Social experiences during adolescence affect anxiety-like behavior but not aggressiveness in male mice.

    Meyer, Neele; Jenikejew, Julia; Richter, S Helene; Kaiser, Sylvia; Sachser, Norbert

    2017-05-30

    Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice

    Amy Ashworth

    2014-12-01

    Full Text Available The C57BL/6 (B6 mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory and B6N substrains (National Institutes of Health; however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM, B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain must be taken into account when designing developmental neurotoxicology studies.

  7. Production of the first offspring from oocytes derived from fresh and cryopreserved pre-antral follicles of adult mice

    Kagawa, Norika; Kuwayama, Masashige; Nakata, Kumiko

    2007-01-01

    transplanted beneath the kidney capsule of severe combined immunodeficient (SCID) mice. Within 10 days of in-vivo culture, 138 full size oocytes developed from the 456 transplanted pre-antral follicles. In-vivo growth of follicles was followed by in-vitro oocyte maturation, in-vitro fertilization...... and subsequent embryo transfer, leading to the birth of 10 healthy pups. These results may lead to increasing the availability and cryopreservation possibilities for the preservation of fertility using ovarian tissue...

  8. Acute endocrine correlates of attack by lactating females in male mice: effects on plasma prolactin, luteinizing hormone and corticosterone levels.

    Broida, J; Michael, S D; Svare, B

    1984-05-01

    Immediately following defeat inflicted by lactating Rockland-Swiss (R-S) albino mice, adult R-S male mice exhibited significant reductions in circulating prolactin (PRL) and luteinizing hormone (LH), but not corticosterone (CORT). These results suggest that acute neuroendocrine responses to intersex competition may be as dramatic as those previously reported for intermale encounters.

  9. Estradiol-induced, endothelial progenitor cell-mediated neovascularization in male mice with hind-limb ischemia

    Ruifrok, Willem-Peter T.; de Boer, Rudolf A.; Iwakura, Atsushi; Silver, Marcy; Kusano, Kengo; Tio, Rene A.; Losordo, Douglas W.

    We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and

  10. Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice.

    Horii, Yasuyuki; Nagasawa, Tatsuhiro; Sakakibara, Hiroyuki; Takahashi, Aki; Tanave, Akira; Matsumoto, Yuki; Nagayama, Hiromichi; Yoshimi, Kazuto; Yasuda, Michiko T; Shimoi, Kayoko; Koide, Tsuyoshi

    2017-08-01

    Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

  11. X-y interactions underlie sperm head abnormality in hybrid male house mice.

    Campbell, Polly; Nachman, Michael W

    2014-04-01

    The genetic basis of hybrid male sterility in house mice is complex, highly polygenic, and strongly X linked. Previous work suggested that there might be interactions between the Mus musculus musculus X and the M. m. domesticus Y with a large negative effect on sperm head morphology in hybrid males with an F1 autosomal background. To test this, we introgressed the M. m. domesticus Y onto a M. m. musculus background and measured the change in sperm morphology, testis weight, and sperm count across early backcross generations and in 11th generation backcross males in which the opportunity for X-autosome incompatibilities is effectively eliminated. We found that abnormality in sperm morphology persists in M. m. domesticus Y introgression males, and that this phenotype is rescued by M. m. domesticus introgressions on the X chromosome. In contrast, the severe reductions in testis weight and sperm count that characterize F1 males were eliminated after one generation of backcrossing. These results indicate that X-Y incompatibilities contribute specifically to sperm morphology. In contrast, X-autosome incompatibilities contribute to low testis weight, low sperm count, and sperm morphology. Restoration of normal testis weight and sperm count in first generation backcross males suggests that a small number of complex incompatibilities between loci on the M. m. musculus X and the M. m. domesticus autosomes underlie F1 male sterility. Together, these results provide insight into the genetic architecture of F1 male sterility and help to explain genome-wide patterns of introgression across the house mouse hybrid zone.

  12. Embryonic effects transmitted by male mice irradiated with 512 MeV/u 56Fe nuclei

    Wiley, L.M.; Van Beek, M.E.A.B.; Raabe, O.G.

    1994-01-01

    High-energy, high-charge nuclei may contribute substantially to the yearly equivalent dose in space flight from galactic cosmic radiation (GCR) at solar minimum. The largest single heavy-ion component is 56 Fe. We used the mouse embryo chimera assay to test 512 MeV/u 56 Fe nuclei for effects on the rate of proliferation of embryonic cells transmitted by sperm from irradiated mice. Male CD1 mice were acutely irradiated with 0.01, 0.05, or 0.1 Gy (LET, 184 keV/μm; fluence, 3.5 x 10 4 -3.3 x 10 5 nuclei/cm 2 ; average dose rate, 0.02 Gy/min) at the Lawrence Berkeley Laboratory BEVATRON/BEVALAC Facility in Berkeley, CA. Irradiated males were bred weekly for 7 weeks to nonirradiated females and their four-cell embryos were paired with control embryos, forming aggregation chimeras. After 30-35 h of culture, chimeras were dissociated to obtain open-quotes proliferation ratiosclose quotes (number of cells contributed by the embryo from the irradiated male/total number of cells in the chimera). Significant dose-dependent decreases in proliferation ratios were obtained across all three dose groups for postirradiation week 2 (P 56 Fe nuclei. However, up to 47% of sperm during postirradiation weeks 1 and 2 transmitted proliferation ratios that were at or below one standard deviation from control mean proliferation ratios. 26 refs., 4 figs., 10 tabs

  13. Age-related and 224Ra-induced abnormalities in the teeth of male mice

    Humphreys, E.R.; Stones, V.A.

    1985-01-01

    A high incidence of incisor abnormalities was found in aged control and aged 224 Ra-treated male CBA mice. Visual examination of the abnormalities in both controls and treated mice revealed extreme shortening of the upper incisors and hypoplastic, grooved or undulating enamel. The administration of 865 or 1730 nCi of 224 Ra hastened the onset of incisor abnormalities although no specific feature was attributable solely to radium toxicity. Radiography and histology revealed corrugated incisors, obliteration of the pulp cavity, extension and disorganized growth of incisors basally, secondary incisors, open pulp and fractures within the alveoli. There was a statistically-significant reduction in the number of molars present in animals given 432, 865 or 1730 nCi 224 Ra. (author)

  14. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  15. Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice.

    Leigh Perreault

    Full Text Available AIMS/HYPOTHESIS: Glucose sensing (eg. glucokinase activity becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly. METHODS: To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5 vs. water alone (n = 5 was administered at the EPA's purported "safe dose" (50 µg/kg by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1-20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15 or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14 for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above. RESULTS: Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002-0.029 at glucose 5-20 mmol/l; overall treatment effect p<0.001. Exposure to BPA over 2 weeks also suppressed hepatic glucokinase activity in exposed vs. unexposed mice (overall treatment effect, p = 0.003. In both experiments, the Hill coefficient was higher and Vmax lower in mice treated with BPA. CONCLUSIONS/INTERPRETATION: Both acute and chronic exposure to BPA significantly impair hepatic glucokinase activity and function. These findings identify a potential mechanism for how BPA may increase risk for diabetes.

  16. Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.

    Thangthaeng, Nopporn; Rutledge, Margaret; Wong, Jessica M; Vann, Philip H; Forster, Michael J; Sumien, Nathalie

    2017-02-01

    Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

  17. Immunotoxicity evaluation of novel bioactive composites in male mice as promising orthopaedic implants

    Gehan T. El-Bassyouni

    2017-05-01

    Full Text Available Objective : In orthopaedics, novel bioactive composites are largely needed to improve the synthetic achievement of the implants. In this work, semiconducting metal oxides such as SiO 2 , TiO 2 , and ZrO 2 particles (Ps were used individually and in different ratios to obtain different biphasic composites. The immunotoxicity of these composites was tested to inspect the potential toxicity prior to their use in further medical applications. Materials and methods : In vitro mineralisation ability was inspected by soaking the composites in simulated body fluid (SBF. Additionally, in vivo experiments were performed consuming male mice using ISSR-PCR, micronucleus (MN test, comet assay, glutathione peroxidase activity, and determination of albumin, globulin, lymphocyte population, ALT, and AST levels. Several groups of adult male albino mice were treated with 100, 200, and 400 mg/kg body weight of SiO 2 , TiO 2 , and ZrO 2 -Ps in pure or mixed forms. Results : Our findings revealed that treatment of mice with low and medium doses of SiO 2 , TiO 2 , and ZrO 2 -Ps in pure or mixed form revealed values relatively similar to the control group. However, using 400 mg/kg especially from TiO 2 -Ps in genuine form or mixed with SiO 2 showed proliferation in the toxicity rates compared with the high dose of SiO 2 and ZrO 2 -Ps. Conclusions : The results suggest that TiO 2 composite induced in vivo toxicity, oxidative DNA damage, bargain of the antioxidant enzymes, and variations in the levels of albumin, globulin, lymphocyte population, ALT, and AST in a dose-dependent manner. However, SiO 2 , and ZrO 2 composites revealed a lower toxicity in mice compared with that of TiO 2 .

  18. Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

    Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun [KAERI, Taejon (Korea, Republic of); Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2003-04-01

    The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector.

  19. Radioprotective effects of shark cartilage mucopolysaccharide preparation on immune nad reproductive organs in male mice

    Luan Jie; Shen Xianrong; Jiang Dingwen; Chen Wei; Lu Min

    2008-01-01

    Objective: To evaluate the protective effects of shark cartilage mucopolysaccharide preparation (SCMP) on immune and reproductive organs in male mice with irradiation damage induced by γ-rays. Methods: 50 mice were randomly divided into normal control group,model control group, the 0.5g/kg. d SCMP group, the 1.0g/kg. d SCMP group, and the 2.0g/kg. d SCMP group. SCMP was administrated by intragastric infusion with the volume of 0.4ml per 20g. Normal control group and model control group were given the same volume of water. 2 weeks later, all of the mice were irradiated by γ-ray of 60 Co(0.83Gy/h) with the dose of 5 Gy. Peripheral blood WBC, the spleen index(SI), thymus index(TI), the gMNC, testicle index, germ cells were detected. Results: Compared with the modal control group, peripheral blood WBC became significantly higher in the treated groups with 1.0g/kg. d and 2.0g/kg. d SCMP after 3 days by irradiation (P<0.05). TI, BMNC and germ cells were significantly higher in the treated groups with 1.0g/kg. d and 2.0g/kg. d SCMP comparing with the control model group (P<0.05) and SI, and Testicle index was significantly compared with the model group (P<0.05) only in 2.0g/ kg. d SCMP treated group. The germ abnormality rate became lower in SCMP treated groups (P<0.01) in 1.0 and 2.0g/kg. d SCMP group. Conclusion: SCMP has radioprotective effects on immune and reproductive organs in male mice. (authors)

  20. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

    Olajumoke Omolara Ojo

    Full Text Available Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR and cytochrome P450 side chain cleavage proteins (CYP11A1 were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of

  1. Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

    Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun; Yoon, Yong Dal

    2003-01-01

    The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector

  2. 241Am distribution and retention in pregnant mice, in their offspring and in non-pregnant mice: comparison between continuous Am administration and single injection

    Huevel, R. Van Den; Vander Plaetse, F.; Leppens, H.; Schoeters, G.

    1992-01-01

    Pregnant BALB/c mice and age and sex matched nulliparous controls were contaminated with 241 Am (13 kBq per mouse). Five days after the termination of contamination, 241 Am incorporation was measured in the tissues of adults and in the liver an the femur of newborn and one-month-old mice. Pregnancy resulted in higher 241 Am concentrations in bone but lower concentrations in the liver of the mothers. Protracted administration of 241 Am compared to a single injection resulted in a lower concentration of 241 Am in the livers of pregnant mice, their nulliparous controls and from newborn mice. The higher 241 Am concentration in the femur at birth after protected exposure before 14 days of gestation compared to protracted exposure after 14 days of gestation could reflect the increased placental transfer of 241 Am with advancing gestational age. Radiation doses to the femur were estimated between 4 and 20 mGy. Haemopoietic changes were noticed at these dose levels in all groups until at least 6 months after birth. (author)

  3. sup 241 Am distribution and retention in pregnant mice, in their offspring and in non-pregnant mice: comparison between continuous Am administration and single injection

    Huevel, R. Van Den; Vander Plaetse, F.; Leppens, H.; Schoeters, G. (Centre d' Etude de l' Energie Nucleaire, Mol (Belgium))

    1992-01-01

    Pregnant BALB/c mice and age and sex matched nulliparous controls were contaminated with {sup 241}Am (13 kBq per mouse). Five days after the termination of contamination, {sup 241}Am incorporation was measured in the tissues of adults and in the liver an the femur of newborn and one-month-old mice. Pregnancy resulted in higher {sup 241}Am concentrations in bone but lower concentrations in the liver of the mothers. Protracted administration of {sup 241}Am compared to a single injection resulted in a lower concentration of {sup 241}Am in the livers of pregnant mice, their nulliparous controls and from newborn mice. The higher {sup 241}Am concentration in the femur at birth after protected exposure before 14 days of gestation compared to protracted exposure after 14 days of gestation could reflect the increased placental transfer of {sup 241}Am with advancing gestational age. Radiation doses to the femur were estimated between 4 and 20 mGy. Haemopoietic changes were noticed at these dose levels in all groups until at least 6 months after birth. (author).

  4. Synergistic induction of tumors in NMRI mice by combined fetal X-irradiation with low doses and ethylnitrosourea administered to juvenile offspring

    Schmahl, W.

    1988-08-01

    Mice were X-irradiated on day 15 of gestation with 0.2, 0.4, 0.8 or 1.6 Gy. Offspring were reared by their mothers and divided into two subgroups at an age of 21 days, one subgroup receiving a single dose (45 mg/kg) of ethylnitrosourea (ENU). All animals were kept ultimately until 22 months to register the long-term tumor pattern. The carcinogenic effects of ENU alone were also studied in two separate experiments. Prenatal X-irradiation with 1.6 Gy mostly abolished the carcinogenic late effects of ENU, with the exception of an almost constant leucosis incidence and an unchanged lung tumor frequency. Lowering the prenatal X-ray dose to 0.8 Gy resulted in a significantly increased rate of liver tumors and ovary tumors. Synergistic effects on various tissues were observed after both 0.4- and 0.2-Gy fetal X-irradiation treatment in combination with postnatal application of ENU. These effects mainly involved a significant increase in the frequency of leucosis and of tumors of the liver, intestine, uterus and ovaries. The greater-than-additive effect in the case of these tumors suggests that low-level prenatal X-irradiation leads to a lasting sensitivity of some tissues towards a subsequent carcinogenic stimulus.

  5. Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice.

    Smarr, Benjamin L; Grant, Azure D; Perez, Luz; Zucker, Irving; Kriegsfeld, Lance J

    2017-06-12

    Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.

  6. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    Fu, Zidong Donna [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160 (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, 66160 (United States)

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  7. Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice.

    Chun Fu

    Full Text Available After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance protein. Fanconi anemia (FA proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2-3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line.

  8. Butyl paraben and propyl paraben modulate bisphenol A and estradiol concentrations in female and male mice

    Pollock, Tyler; Weaver, Rachel E.; Ghasemi, Ramtin; Catanzaro, Denys de, E-mail: decatanz@mcmaster.ca

    2017-06-15

    People are routinely exposed to the antimicrobial preservatives butyl paraben (BP) and propyl paraben (PP), as well as the monomer of polycarbonate plastics, bisphenol A (BPA). These chemicals are reliably detected in human urine and potentially interact. We investigated whether BP or PP exposure can modulate the concentrations of {sup 14}C-BPA and 17β-estradiol (E{sub 2}). Female and male CF1 mice were each given a subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9 mg BP or PP, then given a dietary supplement containing 50 μg/kg {sup 14}C-BPA. Radioactivity was measured in tissues through liquid scintillation counting. Significantly elevated {sup 14}C-BPA concentrations were observed following BP treatment in blood serum of both sexes, as well as the lungs, uterus, and ovaries of females and the testes and epididymides of males. Treatment with PP significantly elevated {sup 14}C-BPA concentrations in the uterus only. In another experiment, female and male CF1 mice were each injected with vehicle, 3 mg BP, or 3 mg PP, and E{sub 2} was measured in urine 2–12 h later. Whereas PP did not affect E{sub 2}, BP significantly elevated E{sub 2} 6–10 h after injection in females and 8 h after injection in males. These data indicate that BP and PP can alter the pharmacokinetics of BPA in vivo, and that BP can modulate E{sub 2} concentrations. These results are consistent with evidence that parabens inhibit enzymes that are critical for BPA and E{sub 2} metabolism, and demonstrate the importance of considering concurrent exposure to multiple chemicals when determining regulatory exposure limits. - Highlights: • We studied whether paraben exposure affects the distribution of oral {sup 14}C-BPA. • Elevated {sup 14}C–BPA was observed in mice given butyl or propyl paraben. • We also studied whether paraben exposure affects natural E{sub 2} levels in urine. • Elevated E{sub 2} was observed in mice given butyl, but not propyl, paraben. • Parabens may

  9. Regulatory divergence of X-linked genes and hybrid male sterility in mice.

    Oka, Ayako; Shiroishi, Toshihiko

    2014-01-01

    Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

  10. Effects of noise pollution stress during pregnancy on anatomical and functional brain cortex development of the offsprings of NMRI mice

    Sara Bijani

    2012-12-01

    Full Text Available Introduction: Effects of stress on changes in neural system activity is well defined, which might be because of the changes in brain cortex architecture. In the present study, the effects of maternal noise stress on the morphological and functional changes in brain cortex of off springs of NMRI mice were examined.Materials and Methods: Female pregnant mice divided into two groups. Control group was maintained in their home cages without any invasion but the experimental group was exposed to the noise stress (80 db for 5 min/day from day zero of pregnancy to day 14 (i.e. 15 days. After delivery, six pups from each group were killed and their brains were fixed, sectioned and stained in H&E. These sections were investigated by MOTIC software for both control and experimental groups. Other pups were nursed by their mothers until their adolescence (22 g-8 weeks old. Then they were examined for behavioral side-biased and locomotor activity tests.Results: Decrease in cortex diameter and diameter of each layer for the experimental group was observed. In addition, neuron counting in each layer indicated that the number of the neurons in the middle and outer layers of cortex for the experimental group was reduced than the control group. In contrast, the number of the neurons in the inner layer of the experimental group was increased. From the functional view, in experimental group increases in left-handness especially in female off springs were observed. Furthermore, spontaneous locomotor activity in the new environment was increased in the experimental group.Conclusion: These results indicated that neuronal immigration and network connections in the inner layer of cortex through the middle and outer layers in the experimental group were inhibited. In other word, noise stress was able to inhibit brain cortex development in next generation

  11. 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.

    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.

  12. 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

    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

  13. A disparity between locomotor economy and territory-holding ability in male house mice.

    Morris, Jeremy S; Ruff, James S; Potts, Wayne K; Carrier, David R

    2017-07-15

    Both economical locomotion and physical fighting are important performance traits to many species because of their direct influence on components of Darwinian fitness. Locomotion represents a substantial portion of the total daily energy budget of many animals. Fighting performance often determines individual reproductive fitness through the means of resource control, social dominance and access to mates. However, phenotypic traits that improve either locomotor economy or fighting ability may diminish performance in the other. Here, we tested for a predicted disparity between locomotor economy and competitive ability in wild-derived house mice ( Mus musculus ). We used 8 week social competition trials in semi-natural enclosures to directly measure male competitive ability through territorial control and female occupancy within territories. We also measured oxygen consumption during locomotion for each mouse using running trials in an enclosed treadmill and open-flow respirometry. Our results show that territory-holding males have higher absolute and mass-specific oxygen consumption when running (i.e. reduced locomotor economy) compared with males that do not control territories. This relationship was present both before and after 8 week competition trials in semi-natural enclosures. This disparity between physical competitive ability and economical locomotion may impose viability costs on males in species for which competition over mates is common and may constrain the evolution of behavioral and phenotypic diversity, particularly in natural settings with environmental and resource variability. © 2017. Published by The Company of Biologists Ltd.

  14. Promotion of hepatic preneoplastic lesions in male B6C3F1 mice by unleaded gasoline.

    Standeven, A M; Wolf, D C; Goldsworthy, T L

    1995-01-01

    In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promoter and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen in male mice. However, UG vapor had similar transient mitogenic effects in nonlesioned liver of both male and female mice under the conditions of the cancer bioassay. We used an initiation-promotion protocol to determine whether UG vapor acts as a liver tumor promoter in male mice and to examine proliferative effects that may be critical to tumor development. Twelve-day-old male B6C3F1 mice were injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5 days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN-initiated mice, whereas no macroscopic masses were observed in non-initiated mice. Altered hepatic foci (AHF), which were predominantly basophilic in phenotype, were found almost exclusively in DEN-initiated mice. UG treatment significantly increased both the mean volume (threefold) and the volume fraction (twofold) of the AHF without increasing the number of AHF per unit area. UG also induced hepatic pentoxyresorufin-O-dealkylase (PROD) activity, a marker of CYP2B, by more than 12-fold over control with or without DEN cotreatment. To study hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2'-deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured hepatocyte BrdU labeling index (LI) in AHF and nonlesioned liver.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. PMID:7588481

  15. Action of the schistosomotic spleen in male mices on the regulation of thyroid hormones

    Neves, S.R.S.; Silva, I.M.S.; Pereira, S.S.L.; Lima Filho, G.L.; Catanho, M.T.J.A.; Neves, E.S.; Silveira, M.F.G.

    1997-01-01

    For the purpose to study the action of the schistosomotic spleen on the regulation of TSH, T4 and albumin levels in serum, spleens from adults mice infected by Schistosoma mansoni were homogeneized, centrifuged and cromatographed in a column of Sephadex G-100, resulting in two proteans fractions (I and II). The biologic activity was determinated through the administration of the fractions by intraperitoneal way (IP), in male mice aged 27-30 days, in a period of three following days. Five days after the last administration, the animals were sacrified and their blood was collected for obtainment of serum and determination of TSH, T4 and albumin levels. Obtained results showed that the albumin levels no change when compared to control and that fraction I infected change the TSH and T4 levels, but the fraction II infected no change this levels. These results suggest that spleens from mice infected by S. mansoni have a factor that modifies the hormonal regulation in level hypophysial and the synthesis of thyroid hormones (T4), changing the basal metabolism. The seric levels of TSH and T4 were determined by radioimmunoassay using I-125. (author). 12 refs., 1 tab

  16. [Genotype-related changes in the reproductive function under social hierarchy in laboratory male mice].

    Osadchuk, L V; Salomacheva, I N; Osadchuk, A V

    2010-01-01

    The study was designed to investigate genetic differences in reproductive consequences of social hierarchy using inbred mice strains BALB/cLac, PT and CBA/Lac. Two adult males of different genotypes were housed together for 5 days. Hierarchical status of both partners was determined by asymmetry in agonistic behavior. The number of epididymal sperm and a proportion of abnormal sperm, weights of reproductive organs, serum concentration and testicular content of testosterone, and the testosterone response to introduction of a receptive female were determined. The testosterone measures were significantly decreased in the PT strain, the epididymal sperm number was significantly decreased in the BALB/cLac strain and a proportion of abnormal sperm heads was significantly increase in the CBA/Lac (in both dominants and subordinates) as compared to control mice. The testicular testosterone response to a receptive female and precopulatory behavior was unchanged in dominants and suppressed in subordinates of the BALB/cLac strain. The results indicate that in laboratory mice the pattern of reproductive response to social hierarchy is determined by genetic background.

  17. Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

    Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

    2015-07-01

    Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

  18. IGF1 stimulates greater muscle hypertrophy in the absence of myostatin in male mice.

    Hennebry, Alexander; Oldham, Jenny; Shavlakadze, Tea; Grounds, Miranda D; Sheard, Philip; Fiorotto, Marta L; Falconer, Shelley; Smith, Heather K; Berry, Carole; Jeanplong, Ferenc; Bracegirdle, Jeremy; Matthews, Kenneth; Nicholas, Gina; Senna-Salerno, Mônica; Watson, Trevor; McMahon, Christopher D

    2017-08-01

    Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null ( Mstn -/- ) mice with mice overexpressing Igf1 in skeletal muscle ( Igf1 + ) to generate six genotypes of male mice; wild type ( Mstn +/+ ), Mstn +/- , Mstn -/- , Mstn +/+ :Igf1 + , Mstn +/- :Igf1 + and Mstn -/- :Igf1 + Overexpression of Igf1 increased the mass of mixed fibre type muscles (e.g. Quadriceps femoris ) by 19% over Mstn +/+ , 33% over Mstn +/- and 49% over Mstn -/- ( P  Myostatin regulated the number, while IGF1 regulated the size of myofibres, and the deletion of Mstn and Igf1 + independently increased the proportion of fast type IIB myosin heavy chain isoforms in T. anterior (up to 10% each, P  myostatin is absent and IGF1 is in excess. Finally, we show that myostatin and IGF1 regulate skeletal muscle size, myofibre type and gonadal fat through distinct mechanisms that involve increasing the total abundance and phosphorylation status of AKT and rpS6. © 2017 Society for Endocrinology.

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

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

    2017-01-01

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

  20. Reproductive, cytological and biochemical toxicity of Yohimbe in male Swiss albino mice.

    Al-Majed, Abdulhakeem A; Al-Yahya, Abdulaziz A; Al-Bekairi, A M; Al-Shabanah, Othman A; Qureshi, Shoeb

    2006-07-01

    To study the effect of Corynanthe Yohimbe (Yohimbe) on germ cells in Swiss albino mice. Adult male mice were orally (gavage) treated with different doses (188, 375 and 750 mg/[kg x day]) of aqueous suspension of Yohimbe for 90 days. The following parameters were evaluated: (i) reproductive organ weight, (ii) motility and count of sperm, (iii) study on rate of pregnancy and mean implants, (iv) spermatozoa morphology, (v) cytology of the testes chromosomes, and (vi) biochemical study on estimation of proteins, RNA, DNA, malondialdehyde, nonprotein sulfhydryl (NP-SH) and hormones. The treatment caused significant increase in the weight of seminal vesicles, motility and count of spermatozoa, pre- and post-implants. Male fertility was decreased. These results are confirmed by our data on spermatozoa abnormalities and chromosomal aberrations. The data on biochemical parameters showed increase of malondialdehyde and depletion of NP-SH, proteins, RNA and DNA in the testicular cells. Our results elucidated the role of free radical species in cytological and reproductive changes, possibly, under the influence of yohimbine (principal constituent of Yohimbe) on neurotransmitters, including norephinephrine. These data warrant careful use of Yohimbe.

  1. Cyclophosphamide-induced male subfertility in mice: An assessment of the potential benefits of Maca supplement.

    Onaolapo, A Y; Oladipo, B P; Onaolapo, O J

    2018-04-01

    Effects of Lepidium meyenii (Maca) on cyclophosphamide (CYP)-induced gonadal toxicity in male mice were investigated. Mice were assigned to six treatment groups: Vehicle control, CYP control, CYP plus oral Maca (500 or 1,000 mg/kg), and oral Maca (500 or 1,000 mg/kg). CYP was administered via the intraperitoneal route (days 1-2), while vehicle or Maca were administered daily for 28 days. On day 28, half of the animals in each group were either sacrificed or paired with age-matched females for fertility assessment. Plasma testosterone assay, sperm analysis and assessment of tissue antioxidant/morphological status were also carried out. CYP administration was associated with oxidative stress, subfertility and morphometric/morphological indices of gonadal injury, while administration of Maca mitigated CYP-induced gonadal toxicity and subfertility. This study shows that Maca is beneficial in the mitigation of CYP-induced male gonadal insufficiency and/or testicular morphological changes; however, further studies will be needed to ascertain its usability for this purpose in humans. © 2017 Blackwell Verlag GmbH.

  2. Effects of 6-mercaptopurine treatment on sperm production and reproductive performance: a study in male mice.

    Ligumsky, Moshe; Badaan, Shadi; Lewis, Hadassa; Meirow, Dror

    2005-04-01

    Azathioprine and 6-mercaptopurine interact in purine metabolism and DNA synthesis, thus their potential mutagenic effects have been of concern in the management of inflammatory bowel disease (IBD), especially in patients of childbearing age. Although several clinical studies have indicated their safety in both reproduction and pregnancy, in a recent large epidemiological study concerns were raised about their adverse effects in pregnant patients with IBD, and experimental or basic data on this subject are limited. The aim of this study was to investigate sperm production, sperm quality, and reproductive outcome following prolonged 6-MP administration to male mice. Highly inbred Balb/c adult male mice were used. 6-MP at doses of 2, 5, and 8 mg/kg (n = 9 for each group) was given daily for 51 days and the treatment group was compared with controls. After 45 days of treatment, the mice were mated with females. Following 13 days of pregnancy, the products of conception were evaluated and live fetuses were examined for gross malformations. Sperm production and morphology were examined after 51 days of 6-MP administration. Treatment with 6-MP at all doses did not affect sperm morphology and sperm production in the testicular tubules, as compared with controls (70% normal sperm). However, pregnancy rates were inversely related to escalating doses of 6-MP: 55%, 41%, 28%, and 16% for control, 2, 5, and 8 mg/kg groups, respectively. Resorption rates (abortions) were 21% in the control group as compared with 45-50% in all the treatment groups, but the incidence of major congenital malformations was not increased. Long-term 6-MP treatment in male mice did not impair sperm production and sperm morphology. However, a significantly high rate of embryonic resorption indicated occult sperm damage. Thus, normal sperm analysis does not necessarily imply that sperm damage at genetic level did not occur. It is difficult to extrapolate from these results to the clinical use of 6-MP

  3. Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice.

    Yi, Xuejie; Gao, Haining; Chen, Dequan; Tang, Donghui; Huang, Wanting; Li, Tao; Ma, Tie; Chang, Bo

    2017-04-01

    To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the P -450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and P -450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function. Copyright © 2017 the American

  4. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    Fatemeh Sheikhbahaei

    2016-12-01

    Full Text Available Background: Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ as a fraction of Nigella sativa on methotrexate (MTX- induced germ cell apoptosis in male mice. Materials and Methods: In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6. A single dose of MTX (20 mg/kg and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results: In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%, apoptotic index (AI; 2.3 ± 0.6%, as well as mRNA expression of p53 (P=0.008, caspase 8 (P=0.002, caspase 3 (P=0.005, caspase 9 (P=0.000, bax (P=0.004 and the ratio of bax/bcl-2 (P=0.000, whereas there was an decrease in the expression of bcl-2 (P=0.003, as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg. Conclusion: TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.

  5. Hippocampal gene expression patterns in oxytocin male knockout mice are related to impaired social interaction.

    Lazzari, Virginia Meneghini; Zimmermann-Peruzatto, Josi Maria; Agnes, Grasiela; Becker, Roberta Oriques; de Moura, Ana Carolina; Almeida, Silvana; Guedes, Renata Padilha; Giovenardi, Marcia

    2017-11-02

    Social interaction between animals is crucial for the survival and life in groups. It is well demonstrated that oxytocin (OT) and vasopressin (AVP) play critical roles in the regulation of social behaviors in mammals, however, other neurotransmitters and hormones are involved in the brain circuitry related to these behaviors. The present study aimed to investigate the gene expression of neurotransmitter receptors in the brain of OT knockout (OTKO) male mice. In this study, we evaluated the expression levels of the OT receptor (Oxtr), AVP receptors 1a and 1b (Avpr1a; Avpr1b), dopamine receptor 2 (Drd2), and the estrogen receptors alpha and beta (Esr1; Esr2) genes in the hippocampus (HPC), olfactory bulb (OB), hypothalamus (HPT) and prefrontal cortex (PFC). AVP gene (Avp) expression was analyzed in the HPT. Gene expression results were discussed regarding to social interaction and sexual behavior findings. Additionally, we analyzed the influence of OT absence on the Avp mRNA expression levels in the HPT. RNA extraction and cDNAs synthesis followed by quantitative polymerase chain reaction were performed for gene expression determination. Results were calculated with the 2 -ΔΔCt method. Our main finding was that HPC is more susceptible to gene expression changes due to the lack of OT. OTKOs exhibited decreased expression of Drd2 and Avpr1b, but increased expression of Oxtr in the HPC. In the PFC, Esr2 was increased. In the HPT, there was a reduced Avp expression in the OTKO group. No differences were detected in the OB and HPT. Despite these changes in gene expression, sexual behavior was not affected. However, OTKO showed higher social investigation and lower aggressive performance than wild-type mice. Our data highlight the importance of OT for proper gene expression of neurotransmitter receptors related to the regulation of social interaction in male mice. Copyright © 2017. Published by Elsevier B.V.

  6. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

    Somers, Christopher M. [University of Regina, Department of Biology, 3737 Wascana Parkway, Regina, SK, S4S 0A2 (Canada)]. E-mail: chris.somers@uregina.ca

    2006-06-25

    Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species.

  7. Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male C57BL/6 mice.

    Ingrao, Joelle C; Johnson, Ron; Tor, Elizabeth; Gu, Yu; Litman, Marcus; Turner, Patricia V

    2013-09-01

    We found that carprofen and meloxicam under 3 environmental conditions (ambient dark, ambient light, and 4 °C) remained stable for at least 7 d. We then evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10 mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking water. Mice did not drink meloxicam-medicated water but readily consumed carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated water per 100 g body weight daily; mice drank more during the dark phase than during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass spectrometry (carprofen) revealed that the peak meloxicam and carprofen concentrations were 16.7 and 20.3 μg/mL and occurred at 4 and 2 h after oral gavage, respectively. Similar blood levels were achieved after 12 h access to the carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.4 mg/L × h, 7.4 h, 0.36 L/kg, and 0.125 mL/h × kg, respectively. Carprofen plasma AUC, elimination half-life, apparent volume of distribution, and apparent oral clearance were 160.8 mg/L × h, 7.4 h, 0.42 L/kg, and 0.062 mL/h × kg, respectively. No gross or microscopic evidence of toxicity was seen in any mouse. Our findings indicate that carprofen can be administered in drinking water to mice and that medicated water bottles should be placed 12 to 24 h prior to painful procedures.

  8. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

    Somers, Christopher M.

    2006-01-01

    Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species

  9. Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice.

    Amiri, Shayan; Haj-Mirzaian, Arya; Momeny, Majid; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Poursaman, Simin; Rastegar, Mojgan; Nikoui, Vahid; Mokhtari, Tahmineh; Ghazi-Khansari, Mahmoud; Hosseini, Mir-Jamal

    2017-01-06

    Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A 2 (cPLA 2 ) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

    Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

    2017-06-01

    Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

  11. Cognitive performance of male and female C57BL/6J mice after repetitive concussive brain injuries.

    Velosky, Alexander G; Tucker, Laura B; Fu, Amanda H; Liu, Jiong; McCabe, Joseph T

    2017-05-01

    In contact sports, repetitive concussive brain injury (rCBI) is the prevalent form of head injury seen in athletes. The need for effective treatment is urgent as rCBI has been associated with a host of cognitive, behavioral and neurological complaints. There has been a growing trend in the use of female animals in pre-clinical research, but few studies have investigated possible sex differences following rCBI. The goal of the current study was to determine any differences between male and female C57BL/6J mice on assessments of learning and memory after repetitive concussive injury. Following rCBI by impact to the scalp, male mice exhibited longer righting reflexes during acute recovery. In both sexes, there were no evident histopathological changes observed in the underlying cerebral cortex or hippocampus. Reactive astrogliosis was elevated in the corpus callosum and optic tract, and astrogliosis was slightly less in the optic tract of female mice. rCBI mice exhibited impairment during the learning phase of the Morris water maze (MWM), but female mice, in comparison to male mice, were observed to have superior spatial memory during standard MWM probe trials. Female mice were overall more active, evidenced by greater distances traveled in the y-maze and greater swim speeds in the MWM. The results of this study demonstrate sex differences in cognitive performance following rCBI and support previous research suggesting the neuroprotective role of sex in brain injury. Published by Elsevier B.V.

  12. Influence of the thymus on the capacity of female mice to reject male skin grafts

    De Pirro, E.S.; Goldberg, E.H.

    1989-01-01

    The ability of female mice to reject H-Y-incompatible, but otherwise histocompatible, male skin grafts differs greatly from strain to strain, as is illustrated particularly by the C57BL strain (B6 and other sublines), termed ''H-Y rejector,'' because females invariably and promptly reject C57BL male skin, in comparison with the C3H strain, termed ''H-Y nonrejector,'' because females characteristically accept male C3H skin. To assess the extent to which the thymus governs this rejector vs. nonrejector status, two studies were made. In the first, lethally irradiated B6 (C57BL) and C3H females were restored with (B6 X C3H)F1 female cells, providing a graft-vs.-host-free milieu for differentiation of the same immunopoietic cell population in B6 vs. C3H hosts. With respect to (B6 X C3H)F1 male skin grafts, B6 hosts responded as rejectors and C3H hosts as nonrejectors, signifying that rejector vs. nonrejector status was determined by the host during immunopoiesis. That the main organ responsible for rejector vs. nonrejector determination is the thymus was shown in a second study. Previously thymectomized (B6 X C3H)F1 females received a histocompatible graft of thymus from either B6 or C3H neonatal females and were restored with donor-marked (B6-Ly-5a X C3H)F1 female cells after lethal irradiation. With respect to (B6 X C3H)F1 male skin grafts, the recipients of B6 thymus grafts responded generally as rejectors and the recipients of C3H thymus grafts responded uniformly as nonrejectors

  13. Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.

    Adekunbi, D A; Li, X F; Lass, G; Shetty, K; Adegoke, O A; Yeo, S H; Colledge, W H; Lightman, S L; O'Byrne, K T

    2018-03-01

    The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV-hSyn-DIO-hM 3 D(Gq)-mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine-N-oxide (CNO). Socio-sexual behaviours were assessed in a counter-balanced fashion after i.p. injection of either saline or CNO (5 mg kg -1 ). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline-treated controls. These data indicate that DREADD-induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour. © 2018 The Authors. Journal of Neuroendocrinology published by John Wiley

  14. Age-Related Decrease in Stress Responsiveness and Proactive Coping in Male Mice.

    Oh, Hee-Jin; Song, Minah; Kim, Young Ki; Bae, Jae Ryong; Cha, Seung-Yun; Bae, Ji Young; Kim, Yeongmin; You, Minsu; Lee, Younpyo; Shim, Jieun; Maeng, Sungho

    2018-01-01

    Coping is a strategic approach to dealing with stressful situations. Those who use proactive coping strategies tend to accept changes and act before changes are expected. In contrast, those who use reactive coping are less flexible and more likely to act in response to changes. However, little research has assessed how coping style changes with age. This study investigated age-related changes in coping strategies and stress responsiveness and the influence of age on the processing of conditioned fear memory in 2-, 12- and 23-month-old male mice. Coping strategy was measured by comparing the escape latency in an active avoidance test and by comparing responses to a shock prod. The results showed that proactivity in coping response gradually decreased with age. Stress responsiveness, measured by stress-induced concentration of corticosterone, was also highest in 2-month-old mice and decreased with age. Consolidation of fear memory was highest in 12-month-old mice and was negatively correlated with the degree of stress responsiveness and proactivity in coping. Fear extinction did not differ among age groups and was not correlated with stress responsiveness or the proactivity of coping. However, the maintenance of extinct fear memory, which was best in 2-month-old mice and worst in 12-month-old mice, was negatively correlated with stress responsiveness but not with coping style. Age-dependent changes in the expression of glucocorticoid receptor (GR) and its regulatory co-chaperones, which are accepted mechanisms for stress hormone stimulation, were measured in the hippocampus. The expression of GR was increased at 12 months compared to other age groups. There were no differences in Hsp70 and BAG1 expression by age. These results can be summarized as follows: (1) stress responsiveness and proactivity in coping decreased with age class; (2) consolidation of fear memory was negatively correlated with both stress responsiveness and proactivity; however, maintenance of

  15. No association of maternal gestational weight gain with offspring blood pressure and hypertension at age 18 years in male sibling-pairs

    Scheers Andersson, Elina; Tynelius, Per; Nohr, Ellen Aagaard

    2015-01-01

    BACKGROUND: Maternal gestational weight gain (GWG) is associated with birth weight, obesity, and possibly blood pressure (BP) and hypertension in the offspring. These associations may however be confounded by genetic and/or shared environmental factors. In contrast to previous studies based on non...

  16. Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2′,4,4′-Tetrabromodiphenyl Ether (BDE-47

    Aser Abrha

    2018-03-01

    Full Text Available For the majority of lipophilic compounds, adipose tissue is traditionally considered as a storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposure may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs are a group of lipophilic flame retardants found in the majority of human samples in North America. Their ability to alter the physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using the RNA-seq approach with subsequent bioinformatic analysis. The expression of genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism was altered in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A, and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.

  17. Maternal and postnatal high-fat diets with high ?6:?3 ratios affect the reproductive performance of male offspring in the mouse.

    Bianconi, S; Stutz, G; Solís, M R; Martini, A C; Vincenti, L M; Ponzio, M F; Luque, E; Avendaño, C; Quiroga, P; Santillán, M E

    2018-05-24

    High-fat diets (HFDs) are an acknowledged risk factor for male subfertility, but the underlying mechanisms remain unclear. In the present study we compared the effects of two HFDs with different ω6:ω3 ratios, one enriched with soy oil (SOD; ω6:ω3=9.62) and another enriched with sunflower oil (SFOD; ω6:ω3=51.55), with those of a commercial diet (CD; ω6:ω3=19.87), supplied from pregnancy to adulthood, on morphometric parameters and reproductive performance in adult male mice (recommended ω6:ω3 for rodents=1-6). Bodyweight was significantly higher in the SFOD than CD group, and relative testicular weight was significantly lower in the SFOD than the other two groups. SFOD altered sperm performance: it reduced sperm viability (mean±s.e.m.; 76.00±1.35% vs 82.50±1.45% and 80.63±1.00% in the SFOD vs CD and SOD groups respectively; P<0.05) and increased the percentage of immature spermatozoa (71.88±7.17% vs 51.38±5.87% and 48.00±5.72% in the SFOD vs CD and SOD groups respectively; P<0.05). The epididymal ω6:ω3 ratio was higher in the SFOD versus CD and SOD groups, whereas the unsaturation index was higher in the SOD and SFOD groups than in CD group. Sperm membrane integrity was diminished in both the SOD and SFOD groups, but there was no difference in sperm reactive oxygen species production in these two groups compared with the CD group. The fertilisation rate was lower in the SFOD compared with the CD and SOD groups. In conclusion, although both HFDs affected sperm quality, the fertilising ability was more altered by the excessive dietary ω6:ω3 ratio than by the net ω6 content.

  18. Interaction between Sex Hormones and Matricaria Chamomilla Hydroalcholic Extract on Motor Activity Behavior in Gonadectomized Male and Female Mice

    H. Raie

    2006-04-01

    Full Text Available Introduction & Objective: Locomotor activity is an important physiologic phenomenon that is influenced by several factors. In previous study we showed that the matricaria chamomilla (chamomile hydroalcholic extract acts differently in male and female mice. Therefore in this study, the role of sex hormones and chamomile hydroalcholic extract were investigated on motor activity behavior in absence of sex glands in adult male and female NMRI mice. Materials and Methods: Gonadectomized male and female mice were divided into groups (seven mice in each group including: receiving testosterone (2 mg/kg S.C., estradiol benzoate (0.1 mg/kg S.C., and progesterone (0.5 mg/kg S.C. with and without hydroalcholic extract of chamomile (50 mg/kg i.p. Motor activity monitor system was used to evaluate locomotor activity parameters (fast and slow activity, fast and slow stereotype activity, fast and slow rearing in all groups. Results: 1 Testosterone had no any effect on motor activity parameters, but extract of chamomile with and without testosterone decreased motor activity parameters in male mice. 2 Estradiol benzoate and chamomile hydroalcholic extract in presence and absence of each other increased locomotor activity parameters in female mice. 3 Progesterone also did not change motor activity parameters in presence and absence of chamomile hydroalcholic extract in female mice. 4 Administration of Estradiol benzoate with progestrone in presence and absence of chamomile hydroalcholic extract did not alter motor activity parameters in female mice. Conclusion: It seems both of the chamomile hydroalcholic extract and estradiol enhance motor activity and probably act through same system and potentiate the effect of each other. Also it seems there are interaction between estradiol and progesterone and also between chamomile extract and progesterone. Testosterone probably did not have any interaction with chamomile extract in locomotor activity.

  19. Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice

    Kiran Chaudhari; Jessica M. Wong; Philip H. Vann; Nathalie Sumien

    2014-01-01

    Purpose: The purpose of this study was to determine if antioxidant supplementation, moderate exercise, and the combination of both treatments could ameliorate cognitive performance in adult mice and whether the apolipoprotein E (APOE) genotype as well as sex could influence the functional outcomes of the treatments. Methods: For a period of 16 weeks, separate groups of male and female mice expressing either the human APOE3 or APOE4 isoforms were fed either a control diet (NIH-31) or the co...

  20. Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

    DEBOER, MARK D.; LI, YONGLI

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the ...

  1. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    Roko Martinić

    2014-08-01

    Full Text Available Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for several different animal disease models. In this group plasma alanine aminotransferase and aspartate aminotransferase enzyme activities, as well as liver necrosis score were significantly reduced in comparison to control animals treated with physiological saline (p > 0.01. The specificity of the peptide hepatoprotection was investigated from the standpoint of the receptor and peptide blockade. It was concluded that Met-enkephalin effects on the liver were mediated via δ and ζ opioid receptors. Genotoxic testing of Met-enkephalin confirmed the safety of the peptide.

  2. The Effects of Dietary Macronutrient Balance on Skin Structure in Aging Male and Female Mice

    McMahon, Aisling C.; Ruohonen, Kari; Raubenheimer, David; Ballard, J. William O.; Le Couteur, David G.; Nicholls, Caroline; Li, Zhe; Maitz, Peter K. M.; Wang, Yiwei; Simpson, Stephen J.

    2016-01-01

    Nutrition influences skin structure; however, a systematic investigation into how energy and macronutrients (protein, carbohydrate and fat) affects the skin has yet to be conducted. We evaluated the associations between macronutrients, energy intake and skin structure in mice fed 25 experimental diets and a control diet for 15 months using the Geometric Framework, a novel method of nutritional analysis. Skin structure was associated with the ratio of dietary macronutrients eaten, not energy intake, and the nature of the effect differed between the sexes. In males, skin structure was primarily associated with protein intake, whereas in females carbohydrate intake was the primary correlate. In both sexes, the dermis and subcutaneous fat thicknesses were inversely proportional. Subcutaneous fat thickness varied positively with fat intake, due to enlarged adipocytes rather than increased adipocyte number. We therefore demonstrated clear interactions between skin structure and macronutrient intakes, with the associations being sex-specific and dependent on dietary macronutrient balance. PMID:27832138

  3. Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

    Fei He

    Full Text Available Disorders of sexual development (DSD encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E18.5 and adult mice revealed shortened anogenital distance (AGD, open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans.

  4. Enantioselective disruption of the endocrine system by Cis-Bifenthrin in the male mice.

    Jin, Yuanxiang; Wang, Jiangcong; Pan, Xiuhong; Miao, Wenyu; Lin, Xiaojian; Wang, Linggang; Fu, Zhengwei

    2015-07-01

    Bifenthrin (BF), as a chiral pyrethroid, is widely used to control field and household pests in China. At present, the commercial BF is a mixed compound containing cis isomers (cis-BF) including two enantiomers of 1R-cis-BF and 1S-cis-BF. In the present study, the two individual cis-BF enantiomers were separated by a preparative supercritical fluid chromatography. Then, four week-old adolescent male ICR mice were orally administered 1R-cis-BF and 1S-cis-BF separately daily for 3 weeks at doses of 0, 7.5 and 15 mg/kg/day, respectively. Results showed that the transcription status of some genes involved in cholesterol synthesis and transport as well as testosterone (T) synthesis in the testes were influenced by cis-BF enantiomers. Especially, we observed that the transcription status of key genes on the pathway of T synthesis including cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxysteroid dehydrogenase (P45017α)) were selectively altered in the testis of mice when treated with 1S-cis-BF, suggesting that it is the possible reason to explain why the lower serum T concentration in 1S-cis-BF treated group. Taken together, it concluded that both of the cis-BF enantiomers have the endocrine disruption activities, while 1S-cis-BF was higher than 1R-cis-BF in mice when exposed during the puberty. The data was helpful to understand the toxicity of cis-BF in mammals under enantiomeric level. © 2014 Wiley Periodicals, Inc.

  5. Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice.

    Wang, Hao; Zhang, Liang; Abel, Glen M; Storm, Daniel R; Xia, Zhengui

    2018-01-01

    Cadmium (Cd) is a heavy metal of high interest to the superfund initiative. Recent epidemiology studies have suggested a possible association between Cd exposure and cognitive as well as olfactory impairments in humans. However, studies in animal models are needed to establish a direct causal relationship between Cd exposure and impairments in cognition and olfaction. This study aims to investigate the toxic effect of Cd on cognition and olfactory function in mice. One group of 8-week-old C57BL/6 male mice was exposed to 3 mg/l Cd (in the form of CdCl2) through drinking water for 20 weeks for behavior tests and final blood Cd concentration analysis. The behavior tests were conducted before, during, and after Cd exposure to analyze the effects of Cd on cognition and olfactory function. Upon completion of behavior tests, blood was collected to measure final blood Cd concentration. Two additional groups of mice were similarly exposed to Cd for 5 or 13 weeks for peak blood Cd concentration measurement. The peak blood Cd concentration was 2.125-2.25 μg/l whereas the final blood Cd concentration was 0.18 μg/l. At this exposure level, Cd impaired hippocampus-dependent learning and memory in novel object location test, T-maze test, and contextual fear memory test. It also caused deficits in short-term olfactory memory and odor-cued olfactory learning and memory. Results in this study demonstrate a direct relationship between Cd exposure and cognitive as well as olfactory impairments in an animal model. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Precopulatory sexual behavior of male mice is changed by the exposure to tannery effluent.

    Quintão, Thales Chagas; Rabelo, Letícia Martins; Alvarez, T G S; Guimarães, A T; Rodrigues, A S L; Cardoso, L S; Ferreira, R O; Malafaia, Guilherme

    2018-03-01

    Although the toxic potential of tannery effluents (TE) is acknowledged, the impacts these residues have on mammals who intake water contaminated with this pollutant are not completely known. Thus, in order to broaden the knowledge about how these contaminants affect the biota, the aim of the current study is to assess different behavioral categories (e.g.: sexual odor preference, opposite-sex attraction, and sexual discrimination) related to the sexual motivation and pre-copulation of male Swiss mice subjected to TE intake for 30 days, at concentrations 0.8% and 22%. The animals were subjected to locomotor performance evaluation through the Basso Mouse Scale (BMS), as well as to the open field (OF), odor preference (OPT), sexual orientation (SOT) and to scent marking tests (SMT) one week before the experiment ended. Our results evidenced that the treatments did not affect the animals' locomotor activity (in OF and BMS) or caused changes compatible to anxiogenic or anxiolytic behavior (in OF). However, mice exposed to TE (at both concentrations) presented discriminatory capacity deficit in the OPT test at the time to distinguish conspecific odors from the same sex, and from the opposite sex. They randomly explored (without preference) males and females, did not responded to stimuli in the SOT test, as well as did not appear capable of detecting female odor (in estrus phase) during the SMT. Thus, the current study was pioneer in evidencing that TE can influence the reproduction and the population dynamics of small rodents who intake water contaminated with the pollutant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Social isolation reduces serotonergic fiber density in the inferior colliculus of female, but not male, mice.

    Keesom, Sarah M; Morningstar, Mitchell D; Sandlain, Rebecca; Wise, Bradley M; Hurley, Laura M

    2018-05-12

    Early-life experiences, including maternal deprivation and social isolation during adolescence, have a profound influence on a range of adult social behaviors. Post-weaning social isolation in rodents influences behavior in part through the alteration of neuromodulatory systems, including the serotonergic system. Of significance to social behavior, the serotonergic system richly innervates brain areas involved in vocal communication, including the auditory system. However, the influence of isolation on serotonergic input to the auditory system remains underexplored. Here, we assess whether 4 weeks of post-weaning individual housing alters serotonergic fiber density in the inferior colliculus (IC), an auditory midbrain nucleus in which serotonin alters auditory-evoked activity. Individually housed male and female mice were compared to conspecifics housed socially in groups of three. Serotonergic projections were subsequently visualized with an antibody to the serotonin transporter, which labels serotonergic fibers with relatively high selectivity. Fiber densities were estimated in the three major subregions of the IC using line-scan intensity analysis. Individually housed female mice showed a significantly reduced fiber density relative to socially housed females, which was accompanied by a lower body weight in individually housed females. In contrast, social isolation did not affect serotonergic fiber density in the IC of males. This finding suggests that sensitivity of the serotonergic system to social isolation is sex-dependent, which could be due to a sex difference in the effect of isolation on psychosocial stress. Since serotonin availability depends on social context, this finding further suggests that social isolation can alter the acute social regulation of auditory processing. Copyright © 2018. Published by Elsevier B.V.

  8. The Effects of Melatonin with Memantin on MPTP-Induced Parkinson Model in Male Mice

    Reza Talebi

    2015-09-01

    Full Text Available Abstract Background: Oxidative stress and severe neuro-excitation have significant effects on pathogenesis of Parkinson’s disease and agents with antioxidant property can potentially prevent these effects. Herein we examined potential protective effects of melatonin as an antioxidant agent and memantine as an uncompetitive receptor of NMDA, on a model of Parkinson’s disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP. Materials and Methods: Male mice were divided into 8 groups with 7 mice in each group: saline, ethanol, melatonin, memantin, MPTP, melatonin+MPTP, memantin+ MPTP, melatonin+ memantin+ MPTP. All of agents were injected intraperitoneally once a day for 14 days before beam traversal test. Dopaminergic neurons of the Substantia Nigra Pars compacta (SNPC were determined by immunohistochemical and were counted. Results: Melatonin improved notably movement dysfunction resulted of MPTP such as the number of errors, paces and the time of movement during behavioral test and also the counting of neurons of Substantia Nigra Pars Compacta. Memantin had a synergic effect on the most of improvements. However, the level of improvement and retrieval of signs was not as in saline and ethanol groups. Conclusion: Melatonin especially together with memantine is able to prevent some of the MPTP-induced dysfunctions. However, the protective effects were not enogh, probably because of the amount of dose and the time of injection.

  9. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  10. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

    Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

    2016-02-01

    The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

  11. Evaluation of low intensity laser effects in the thyroid glands region of male mice

    Azevedo, Luciane Hiramatsu

    2002-01-01

    Recent studies have demonstrated that the infra-red laser can cause alterations in thyroid glands. Their normal activity must be preserved, as they produce the thyroidal hormones triiodothyronine (T 3 ) and thyroxine (T 4 ), that stimulate the oxidative metabolism, essential to maintain a healthy organism. The increase or diminution of these hormones results in alteration of the mitochondria's activity, that determines the secondary effects in the metabolism. The purpose of this study was to evaluate if there was any alteration of the thyroidal hormones plasma levels under irradiation from infra-red laser, with energy density of 4J/cm 2 , in the region of thyroid glands of male mice. It was concluded that there was an hormonal level alteration statistically significant between the first day of irradiation and seven days after the last application. Histological studies showed that there was no morphological changes in histological sections of thyroid glands. The optical absorption spectroscopy of mice's serum presented a peak at approximately 280 nm, attributed to tyrosine (this is the amino acid compounding these hormones). (author)

  12. Middle age has a significant impact on gene expression during skin wound healing in male mice.

    Yanai, Hagai; Lumenta, David Benjamin; Vierlinger, Klemens; Hofner, Manuela; Kitzinger, Hugo-Benito; Kamolz, Lars-Peter; Nöhammer, Christa; Chilosi, Marco; Fraifeld, Vadim E

    2016-08-01

    The vast majority of research on the impact of age on skin wound healing (WH) compares old animals to young ones. The middle age is often ignored in biogerontological research despite the fact that many functions that decline in an age-dependent manner have starting points in mid-life. With this in mind, we examined gene expression patterns during skin WH in late middle-aged versus young adult male mice, using the head and back punch models. The rationale behind this study was that the impact of age would first be detectable at the transcriptional level. We pinpointed several pathways which were over-activated in the middle-aged mice, both in the intact skin and during WH. Among them were various metabolic, immune-inflammatory and growth-promoting pathways. These transcriptional changes were much more pronounced in the head than in the back. In summary, the middle age has a significant impact on gene expression in intact and healing skin. It seems that the head punch model is more sensitive to the effect of age than the back model, and we suggest that it should be more widely applied in aging research on wound healing.

  13. Gonadal cell kinetics in male mice treated with sulphur-35 during prenatal development

    Satyanarayana Reddy, K.; Reddy, P.P.; Reddi, O.S.

    1980-01-01

    Investigations on the possible hazards of the use of internally administered radioisotopes in human medicine either as therapeutic or diagnostic agents before or during child bearing age are of late gaining importance. The present investigation has been taken up to screen the effects of sulphur-35 on spermatogonia. CBA pregnant mice were injected (ip) with a dose of 20 μ Ci of sulphur-35 on 3.5, 10.5 or 15.5 days of gestation. At the similar intervals pregnant mice injected with physiological saline were kept for control data. All the animals were allowed to litter and F 1 male progeny were killed at maturity at the age of 10 weeks and the testes collected. Sections of both the testes were prepared and stained by PAS-haematoxylin technique and the survival of spermatogonia types A, Int and B and preleptotene spermatocytes was evaluated. There was a significant reduction in all the cell types in the sulphur-35 treated animals. Thus the results indicate the cell-killing effect of radionuclide. (auth.)

  14. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    Motoi Tamura

    2013-12-01

    Full Text Available This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group and those fed a 0.05% daidzein-containing control diet (CD group for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05. Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05. The fecal lipid contents (% dry weight were significantly greater in the XD group than in the CD group (p < 0.01. The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05. This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health.

  15. Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

    Dreau, Didier; Morton, Darla S.; Foster, Mareva; Swiggett, Jeanene P.; Sonnenfeld, Gerald

    1995-01-01

    Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

  16. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-12-10

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p XD group than in the CD group (p XD group than in the CD group (p XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health.

  17. Gonadal cell kinetics in male mice treated with sulphur-35 during prenatal development

    Satyanarayana Reddy, K; Reddy, P P; Reddi, O S [Osmania Univ., Hyderabad (India). Inst. of Genetics

    1980-11-01

    Investigations on the possible hazards of the use of internally administered radioisotopes in human medicine either as therapeutic or diagnostic agents before or during child bearing age are of late gaining importance. The present investigation has been taken up to screen the effects of sulphur-35 on spermatogonia. CBA pregnant mice were injected (ip) with a dose of 20 ..mu.. Ci of sulphur-35 on 3.5, 10.5 or 15.5 days of gestation. At the similar intervals pregnant mice injected with physiological saline were kept for control data. All the animals were allowed to litter and F/sub 1/ male progeny were killed at maturity at the age of 10 weeks and the testes collected. Sections of both the testes were prepared and stained by PAS-haematoxylin technique and the survival of spermatogonia types A, Int and B and preleptotene spermatocytes was evaluated. There was a significant reduction in all the cell types in the sulphur-35 treated animals. Thus the results indicate the cell-killing effect of radionuclide.

  18. Pairmate-dependent pup retrieval as parental behavior in male mice

    Mingkun eLiang

    2014-07-01

    Full Text Available Appropriate parental care by fathers can greatly facilitate healthy human family life. However, much less is known about paternal behavior in animals compared to those regarding maternal behavior. Previously, we reported that male ICR strain laboratory mice, although not spontaneously parental, can be induced to display maternal-like parental care (pup retrieval when separated from their pups by signals from the pairmate dam (Liu et al., Nat. Commun, 4:1346, 2013. This parental behavior by the ICR sires, which are not genetically biparental, is novel and has been designated as pairmate-dependent paternal behavior. However, the factors critical for this paternal behavior are unclear. Here, we report that the pairmate-dependent paternal retrieval behavior is observed especially in the ICR strain and not in C57BL/6 or BALB/c mice. An ICR sire displays retrieval behavior only toward his biological pups. A sire co-housed with an unrelated non-pairing dam in a new environment, under which 38-kHz ultrasonic vocalizations are not detected, does not show parenting behavior. It is important for sires to establish their own home territory (cage by continuous housing and testing to display retrieval behavior. These results indicated that the ICR sires display distinct paternity, including father-child social interaction, and shed light on parental behavior, although further analyses of paternal care at the neuroendocrinological and neurocircuitry levels are required.

  19. Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we...... investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects...

  20. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    Alessandro Ieraci

    2016-01-01

    Full Text Available Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

  1. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

    Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

    2015-05-01

    Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  2. Neonatal androgenization of hypogonadal (hpg male mice does not abolish estradiol-induced FSH production and spermatogenesis

    Kerr Jeffrey B

    2005-09-01

    Full Text Available Abstract Background Testicular development is arrested in the hypogonadal (hpg mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Methods Hpg mice were treated with 100 μg testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. Results The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Conclusion The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and

  3. Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

    Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-08-01

    The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs.

  4. Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

    Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-08-01

    The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs

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

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

    2006-01-01

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

  6. Diclofenac sex-divergent drug-drug interaction with Sunitinib: pharmacokinetics and tissue distribution in male and female mice.

    Chew, Chii Chii; Ng, Salby; Chee, Yun Lee; Koo, Teng Wai; Liew, Ming Hui; Chee, Evelyn Li-Ching; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L; Segarra, Ignacio

    2017-08-01

    Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC 0→∞ 38% in plasma (p diclofenac increased the liver uptake efficiency in male (27%, p diclofenac with probable clinical translatability due to potential different effects in male and female patients requiring careful selection of the NSAID and advanced TDM to implement a personalized treatment.

  7. Long-term Effects of Dexamethasone on Reproductive Parameters in Male Mice

    jalogoden Gouyandeh

    2015-02-01

    Full Text Available Background & aim: The adverse effect of chemical drugs such as dexamethasone as anti-inflammatory -steroidal drugs on different body systems and infertility and reproductive efficiency is of concern. The purpose of this study was to evaluate the long-term effects of dexamethasone on the reproductive system in male rats. Methods: In the present experimental study, fifty matured male mice were divided into five groups including control, placebo and three treatment groups. Control group had no injections, placebo group only received normal saline and treatments groups received dexamethasone (0.1, 0.5 and 1 mg/kg which was injected in peritoneum every other day for a period of twenty days. Their Testosterone was measured by ELISA and testes were dissected for histological examination. The data were analyzed using SPSS 11.5 software. Results: Significant increases were shown in FSH level in all three groups treated with dexamethasone. LH in treatment group of 0.1 mg/kg decreased, but at dose of 1 mg/kg increased significantly.Testosterone levels in a dose of 1 mg/kg significantly increased compared with the control group (p<0.05. However, testis weight, the rate of testicular germ cells, primary spermatocytes, epididymal sperm and fertility significantly increased in all three groups (p<0.05. Conclusion: Dexamethasone had a negative effect on reproduction therefore, the use of this medication at different doses and time periods considers the possible complications beforehand. Keywords: .

  8. Effects of intermediate frequency magnetic fields on male fertility indicators in mice.

    Kumari, K; Capstick, M; Cassara, A M; Herrala, M; Koivisto, H; Naarala, J; Tanila, H; Viluksela, M; Juutilainen, J

    2017-08-01

    Human exposure to intermediate frequency (IF) fields is increasing due to new applications such as electronic article surveillance systems, wireless power transfer and induction heating cookers. However, limited data is available on effects of IF magnetic fields (MF) on male fertility function. This study was conducted to assess possible effects on fertility indicators from exposure to IF MF. Male C57BL/6J mice were exposed continuously for 5 weeks to 7.5kHz MF at 12 and 120μT. Sperm cells from cauda epididymis were analysed for motility, total sperm counts, and head abnormalities. Motile sperm cells were classified as progressive or non-progressive. Testicular spermatid heads were counted as well. The body weight development and reproductive tissue weights were not affected. No exposure-related differences were observed in sperm counts or sperm head abnormalities. Proportion of non-motile cells was significantly decreased in the 120µT group, and a corresponding increase was seen in the percentage of motile cells (significant in non-progressive motile cells). In conclusion, no adverse effects on fertility indicators were observed. Increased sperm motility is an interesting finding that needs to be confirmed in further studies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice.

    Zhao, Liang; Arsenault, Michel; Ng, Ee Ting; Longmuss, Enya; Chau, Tevin Chui-Ying; Hartwig, Sunny; Koopman, Peter

    2017-03-01

    The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

    2017-01-01

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

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

    Sarah J Glastras

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

  12. Neural androgen receptors affect the number of surviving new neurones in the adult dentate gyrus of male mice.

    Swift-Gallant, A; Duarte-Guterman, P; Hamson, D K; Ibrahim, M; Monks, D A; Galea, L A M

    2018-04-01

    Adult hippocampal neurogenesis occurs in many mammalian species. In rats, the survival of new neurones within the hippocampus is modulated by the action of androgen via the androgen receptor (AR); however, it is not known whether this holds true in mice. Furthermore, the evidence is mixed regarding whether androgens act in neural tissue or via peripheral non-neural targets to promote new neurone survival in the hippocampus. We evaluated whether the action of androgen via AR underlies the survival of new neurones in mice, and investigated whether increasing AR selectively in neural tissue would increase new neurone survival in the hippocampus. We used the cre-loxP system to overexpress AR only in neural tissues (Nestin-AR). These males were compared with wild-type males, as well as control males with 1 of the 2 mutations required for overexpression. Mice were gonadectomised and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU) and for 37 days (following BrdU injection), mice were treated with oil or dihydrotestosterone (DHT). Using immunohistochemistry, proliferation (Ki67) and survival (BrdU) of new neurones were both evaluated in the dorsal and ventral dentate gyrus. Dihydrotestosterone treatment increased the survival of new neurones in the entire hippocampus in wild-type mice and control mice that only have 1 of 2 necessary mutations for transgenic expression. However, DHT treatment did not increase the survival of new neurones in mice that overexpressed AR in neural tissue. Cell proliferation (Ki67) and cell death (pyknotic cells) were not affected by DHT treatment in wild-type or transgenic males. These results suggest that androgens act via neural AR to affect hippocampal neurogenesis by promoting cell survival; however, the relationship between androgen dose and new neurone survival is nonlinear. © 2018 British Society for Neuroendocrinology.

  13. Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice.

    Marshall, Christopher J; Desroziers, Elodie; McLennan, Timothy; Campbell, Rebecca E

    2017-01-01

    Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. GABA neurons rarely co-localized with kisspeptin (95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons. © 2016 S. Karger AG, Basel.

  14. Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice.

    Masaki, Hidetake; Kim, Namhyo; Nakamura, Hitomi; Kumasawa, Keiichi; Kamata, Eriko; Hirano, Ken-Ichi; Kimura, Tadashi

    2017-07-01

    Does the deletion of adipose triglyceride lipase (Atgl) gene impair male fertility? The deletion of Atgl gene impaired male fertility but the effect was partially reversed by a low long-chain triglyceride (TG) diet. ATGL specifically hydrolyses long-chain fatty acid TG to diacylglycerol and a high level of expression of ATGL in testes has been reported. However, the role of ATGL in male fertility is unknown. To investigate the effect of deletion of Atgl gene on male fertility, cauda epididymides and testes were collected from wild-type, heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal sperm analysis and histological analysis of the testes were performed. To investigate whether a medium-chain triglycerides (MCTs) replacement diet mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl-deficient mice were fed a MCT replacement diet, or a standard diet including long-chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n = 22). The systematic and local effects of the MCT replacement diet on spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks of age. Hematoxylin and eosin staining in paraffin-embedded sections of testes and Oil Red O staining in frozen sections of testes were performed. The epididymal sperm concentrations were analyzed. Statistical analyses were performed using the Student's t-test or Mann-Whitney U test with Shapiro-Wilk Normality test. Although heterozygous mice were fertile and showed a similar number of epididymal total and motile sperm concentrations to wild-type mice, the deletion of Atgl gene in homozygous mice led to accumulation of TG deposits in testes and impaired spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation process required for sperm to acquire the ability to move forward in the epididymis. The MCT replacement diet for 6 weeks increased the plasma level of non-esterified fatty acid (NEFA) (1

  15. A Simplified Method for Three-Dimensional (3-D Ovarian Tissue Culture Yielding Oocytes Competent to Produce Full-Term Offspring in Mice.

    Carolyn M Higuchi

    Full Text Available In vitro growth of follicles is a promising technology to generate large quantities of competent oocytes from immature follicles and could expand the potential of assisted reproductive technologies (ART. Isolated follicle culture is currently the primary method used to develop and mature follicles in vitro. However, this procedure typically requires complicated, time-consuming procedures, as well as destruction of the normal ovarian microenvironment. Here we describe a simplified 3-D ovarian culture system that can be used to mature multilayered secondary follicles into antral follicles, generating developmentally competent oocytes in vitro. Ovaries recovered from mice at 14 days of age were cut into 8 pieces and placed onto a thick Matrigel drop (3-D culture for 10 days of culture. As a control, ovarian pieces were cultured on a membrane filter without any Matrigel drop (Membrane culture. We also evaluated the effect of activin A treatment on follicle growth within the ovarian pieces with or without Matrigel support. Thus we tested four different culture conditions: C (Membrane/activin-, A (Membrane/activin+, M (Matrigel/activin-, and M+A (Matrigel/activin+. We found that the cultured follicles and oocytes steadily increased in size regardless of the culture condition used. However, antral cavity formation occurred only in the follicles grown in the 3-D culture system (M, M+A. Following ovarian tissue culture, full-grown GV oocytes were isolated from the larger follicles to evaluate their developmental competence by subjecting them to in vitro maturation (IVM and in vitro fertilization (IVF. Maturation and fertilization rates were higher using oocytes grown in 3-D culture (M, M+A than with those grown in membrane culture (C, A. In particular, activin A treatment further improved 3-D culture (M+A success. Following IVF, two-cell embryos were transferred to recipients to generate full-term offspring. In summary, this simple and easy 3-D ovarian

  16. Effects of tartrazine on exploratory behavior in a three-generation toxicity study in mice.

    Tanaka, Toyohito; Takahashi, Osamu; Oishi, Shinshi; Ogata, Akio

    2008-10-01

    Tartrazine was given to mice in the diet at levels of 0 (control), 0.05%, 0.15%, and 0.45% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(2) generation, and selected reproductive and neurobehavioral parameters were measured. In the F(1) generation, the development of swimming direction at postnatal day (PND) 7 was accelerated significantly in male offspring in a dose-related manner. Surface righting at PND 7 was affected significantly in female offspring in dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age. In the F(2) generation, the development of swimming direction at PND 7 was accelerated significantly in the high-dosed group in male offspring. Time taken of olfactory orientation at PND 14 was accelerated significantly in male offspring in a dose-related manner. Several variables in exploratory behavior showed significant tendencies to be affected in the treatment groups in male offspring at 3 weeks of age, and in males at 8 weeks of age. The dose levels of tartrazine in the present study produced a few adverse effects on neurobehavioral parameters throughout generations in mice.

  17. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice

    Shih-Yin Tsai

    2016-08-01

    Full Text Available Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism.

  18. The Accessory Olfactory System Facilitates the Recovery of the Attraction to Familiar Volatile Female Odors in Male Mice.

    Muroi, Yoshikage; Nishimura, Masakazu; Ishii, Toshiaki

    2017-10-31

    Odors in female mice induce sexual arousal in male mice. Repeated exposure to female odors attenuates male attraction, which recovers when the odors are removed. The neuronal mechanisms for the recovery of male attraction have not been clarified. In this study, we examined how olfactory systems are involved in the recovery of male attraction to female odors following habituation in mice. Presentation with volatile female odors for 5 min induced habituation in males. To evaluate male attraction to familiar volatile female odors, we measured the duration for investigating volatile female odors from the same female mouse, which was presented twice for 5 min with 1-, 3-, or 5-min interval. Intranasal irrigation with ZnSO4 solution almost completely suppressed investigating behavior, indicating that the main olfactory system is indispensable for inducing the attraction to volatile female odors. In contrast, removal of the vomeronasal organ, bilateral lesions of the accessory olfactory bulb (AOB), or pharmacological blockage of neurotransmission in the AOB did not affect the investigation time at the first odor presentation. However, each one of the treatments decreased the investigation time in the second presentation, compared to that in the first presentation, at longer intervals than control treatment, indicating that the disturbance of neurotransmission in the accessory olfactory system delayed the recovery of the attraction attenuated by the first presentation. These results suggest that the accessory olfactory system facilitates the recovery of the attraction to familiar volatile female odors in male mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Evaluation of the effect of soybean diet on interferon-α-induced depression in male mice

    Yazdan Azimi Fashi

    2017-08-01

    Full Text Available Objective: Interferon-α (IFN therapy can cause depressive symptom which may lead to drug discontinuation. By interfering with tryptophan pathway, the available level of tryptophan required for serotonin synthesis decreases which could be related to depression. The aim of this study was to evaluate whether soybean diet could improve IFN-induced depression. Materials and Methods: Male mice weighing 28±3 g were used in the forced swimming test (FST as an animal model of depression; also, locomotor activity was recorded. IFN 16×105 IU/kg was injected subcutaneously for 6 days. Animals were fed with regular diet or soybean diet at 3 concentrations throughout the experiment. Fluoxetine was the reference drug. To check whether the tryptophan content in the soy bean diet was effective, a group of animals was injected with a single dose of tryptophan on the test day. Results: IFN-α increased the immobility time in the FST (192 sec ± 5.4, that denotes depression in mice. Soybean diets caused less immobility that was more profound with 50% soybean (26.4 sec ± 6. This diet overcame the depression caused by IFN in the FST (54 sec±18. This result was parallel with that of tryptophan injected to animals (38 sec±17. All the animals showed normal locomotor activity. Conclusion: For the first time, we showed that soybean diet could counteract with depression caused by IFN-α. Since tryptophan therapy had similar effects, possibly the tryptophan content of soybean had induced the serotonin synthesis. Thus, not only less harmful kynurenine was produced but also more serotonin was available in the brain to overcome depression. However, this interpretation needs further evaluations.

  20. First Chemical Evaluation and Toxicity of Casinga-cheirosa to Balb-c Male Mice

    Dirce M. Estork

    2014-04-01

    Full Text Available Laetia suaveolens, known as “casinga-cheirosa”, crude extract EB719 has previously shown cytotoxic activity against prostate cancer and squamous cell carcinoma. For the first time, seven molecules were isolated from its apolar—α-tocopherol (1 and sitosterol (2—and polar—3-O-caffeoylquinic acid (3, 4-O-caffeoylquinic acid (4, 5-O-feruloylquinic acid (5, hyperoside (6, and isoquercitrin (7—fractions. Acute toxicity was determined in a two-stage experiment: (1 a reduced number of Balb-c male mice received 5000 mg/kg of EB719 to allow evaluation of general activity and other 27 parameters, plus death, up to the establishment of non-lethal dose (NLD, as well as lethal dose 50% (LD50; (2 NLD was administered and diazepam introduced as reference drug. EB719 showed LD50 = 178.0 mg/kg, and NLD 156.3 mg/kg. In stage one EB719 did not influence general activity, but provoked impairment in grasp reflexes, tail squeeze and breathing; piloerection and cyanosis were increased. In stage two, alterations occurred in auricular reflex, piloerection and breathing after diazepam administration, but not in response to EB719. Intestinal hemorrhage caused by local bleeding was observed after necropsy, and may be the main cause of animals’ death other than a systemic effect of the extract. Although the isolated compounds are biologically and pharmacologically active in both men and animal systems, it is premature to relate their occurrence in EB719 to the observed intestine hemorrhage in mice.

  1. Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice.

    Zhang, Yong; Liu, Hong; Li, Wei; Zhang, Zhengang; Shang, Xuejun; Zhang, David; Li, Yuhong; Zhang, Shiyang; Liu, Junpin; Hess, Rex A; Pazour, Gregory J; Zhang, Zhibing

    2017-12-01

    Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27: Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survived to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymides contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the "9+2″ axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the

  2. Intraflagellar Transporter Protein (IFT27), an IFT25 binding partner, Is Essential For Male Fertility and Spermiogenesis In Mice

    Zhang, Yong; Liu, Hong; Li, Wei; Zhang, Zhengang; Shang, Xuejun; Zhang, David; Li, Yuhong; Zhang, Shiyang; Liu, Junpin; Hess, Rex A; Pazour, Gregory J; Zhang, Zhibing

    2017-01-01

    Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27:Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survive to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymis contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the “9+2” axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the conditional

  3. Radio -Protective Role of Zinc Administration Pre-Exposure to Gamma-Irradiation in Male Albino Mice

    El-Dawy, H.A.; Aly El-Sayed, S.M.

    2004-01-01

    This study was performed to evaluate the potency of zinc chloride injected subcutaneously (30 mg/kg b.w.) in male albino mice as a radio-protective agent pre exposure to gamma-irradiation. The investigation of the radio-protective role of zinc chloride was accomplished through measuring the levels of sex hormones, and observation of the chromosomal aberrations and sperm-head abnormalities after exposure to gamma-irradiation. The average of abnormal cells with chromosomal aberration and abnormal sperm % on the 7 th and 21 th days were 32% and 40%, and 14% and 22% respectively in mice exposed to radiation alone compared to 12% and 16%, and 5% and 12% respectively in mice treated with zinc chloride pre-irradiation. Treatment of mice with zinc chloride pre-irradiation induced significant amelioration in FSH and LH hormone levels on the 7 th day only of experimentation period, and showed non-significant amelioration in testosterone level

  4. Distribution of [14C]acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography

    Marlowe, C.; Clark, M.J.; Mast, R.W.; Friedman, M.A.; Waddell, W.J.

    1986-01-01

    Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg [2,3-14C]acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3 hr; renal and hepatic