Pubertal exposure to estrogenic chemicals affects behavior in juvenile and adult male rats

In this paper, we tested the hypothesis that exposure to estrogens of different source and estrogenic potency at early puberty could affect the development of socio-sexual behavior in the male rat. Puberty is regarded as a second stage of the ontogenetic period, in the sexual maturation of mammals, particularly sensitive to gonadal hormone milieu. We treated animals orally, from postnatal day 23 to 30, with an environmentally compatible dose of bisphenol A (BPA, 40 microg/kg/day) and with a dosage of ethinylestradiol (EE, 0.4 microg/kg/day) comparable to the human oral contraceptives. Exposure to EE altered the temporal pattern of male sexual activity, reducing performance, in the adult animals; slight modifications, in the same direction, were observed with BPA. Short-term behavioral effects were observed in the treated animals, both with BPA and EE: the exploratory drive, directed to a stimulus object and to the environment, as well as to conspecifics, was reduced in the juveniles. Modifications in the circulating T levels were observed after treatments: T was reduced in the juveniles, both with BPA and EE. The decrement persisted in the adult animals but reached significance only in the BPA group. On the whole, effects of pubertal exposure on behavior are more marked with EE than BPA. This can be due to the much higher estrogenic potency of EE; the direction of the behavioral effects of BPA, compared with EE, is however indicative of an estrogenic mechanism.     

妊娠期和哺乳期双酚A暴露对幼年子代小鼠焦虑和抑郁行为的影响

双酚A(bisphenol-A,BPA)对脑和行为发育的低剂量效应已引起广泛关注。本研究分别于妊娠最后2周和分娩后前2周母鼠灌胃BPA(0.4和4 mg/kg.d),然后以旷场、高架十字迷宫、明暗箱、镜子迷宫、强迫游泳和被动回避箱等模型,分别测试幼年期(生后21～28 d)子代小鼠的行为,探讨围生期不同阶段的BPA暴露对幼年仔鼠自发活动、探究、焦虑、抑郁和被动回避记忆等行为的影响。结果表明,围生期不同阶段的BPA暴露对这些行为的影响不同,主要表现为:妊娠期BPA暴露促进幼年仔鼠的活动性,减弱其焦虑状态,提高雄性仔鼠的探究能力,促进雌性仔鼠的被动回避记忆;哺乳期BPA暴露减少幼年仔鼠的活动性,但对其焦虑行为的影响相对较弱,不影响仔鼠的探究能力和被动回避记忆;而妊娠期和哺乳期BPA暴露均加剧幼年仔鼠的抑郁行为。以上结果提示,妊娠期和哺乳期BPA暴露均可影响幼年仔鼠的焦虑、抑郁、被动回避记忆等多种行为,而妊娠期可能是BPA影响的更敏感时期。     

Effects of prenatal exposure to low doses of diethylstilbestrol, o,p'DDT, and methoxychlor on postnatal growth and neurobehavioral development in male and female mice

We examined effects of a wide range of doses of three man-made estrogenic chemicals during fetal life on neurobehavioral changes during early postnatal life in mice. Pregnant mice were fed a 4-log range of o,p'DDT, methoxychlor (MXC), and the drug diethystilbestrol (DES) from gestation days 11 to 17. Offspring were examined for changes in postnatal growth and the development of neuromuscular reflexes. Fetal exposure to the estrogenic chemicals altered the number of live pups per litter, the sex ratio of the litters, the anogenital distance of male and female offspring at birth (a bioassay for fetal androgen action), and the body weight of offspring at birth and during the first 5 days of postnatal life. In most cases, however, the dose-response relationships were complex (non-monotonic), with effects at the highest dose examined being opposite to effects seen at lower doses. The two markers of neurobehavioral development, righting and cliff avoidance reflexes, were not sensitive indicators of prenatal estrogen exposure. Only maternal exposure to the lowest MXC dose produced an increase in reactivity in righting and cliff avoidance tests in offspring.     

Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs

Recent findings in the field of environmental endocrine disruption have revealed that developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. The aim of the present study was to determine the effects of in utero exposure to low doses of the estrogenic chemical bisphenol A (BPA) on the development of the female reproductive tissues and mammary glands in CD-1 mice. Humans are exposed to BPA, which leaches from dental materials and plastic food and beverage containers. Here we report that prenatal exposure to BPA induces alterations in tissue organization within the ovaries and mammary glands and disrupts estrous cyclicity in adulthood. Because estrogen receptors are expressed developmentally in these estrogen-target organs, we propose that BPA may directly affect the expression of genes involved in their morphogenesis. In addition, alterations in the sexual differentiation of the brain, and thus the hypothalamic-pituitary-gonadal axis, may further contribute to the observed phenotype. The emerging field of endocrine disruptors promises to provide new insights into the mechanisms underlying the development of hormone-target organs and demonstrates that the environment plays important roles in the making of phenotypes.     

Bisphenol A Does Not Affect Memory Performance in Adult Male Rats

Bisphenol A (BPA) is an estrogenic endocrine disruptor used for producing polycarbonate plastics and epoxy resins. This study investigated the effects of oral BPA administration on memory performance, general activity, and emotionality in adult male Sprague Dawley rats using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) used to assess spatial memory performance. In addition, in order to confirm the effects of BPA on spatial memory performance, we examined whether intrahippocampal injection of BPA affects spatial memory consolidation. In the MAZE test, although oral BPA administration at 10 mg/kg significantly altered the number of entries into the incorrect area compared to those of vehicle-treated rats, male rats given BPA through either oral administration or intrahippocampal injection failed to show significant differences in latencies to reach the reward. Also, oral BPA administration did not affect fear-motivated memory performance in the step-through passive avoidance test. Oral BPA administration at 0.05 mg/kg, the lowest dose used in this study, was correlated with a decrease in locomotor activity in the open-field test, whereas oral administration at 10 mg/kg, the highest dose used in this study, was correlated with a light anxiolytic effect in the elevated plus-maze test. The present study suggests that BPA in adulthood has little effect on spatial memory performance in male rats.     

Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract

Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of in utero exposure to low, environmentally relevant doses of BPA on the development of female reproductive tissues in CD-1 mice. In previous publications, we have shown that this treatment alters the morphology of the mammary gland and affects estrous cyclicity. Here we report that in utero exposure to 25 and 250 ng BPA/ kg of body weight per day via osmotic pumps implanted into pregnant dams at Gestational Day 9 induces alterations in the genital tract of female offspring that are revealed during adulthood. They include decreased wet weight of the vagina, decreased volume of the endometrial lamina propria, increased incorporation of bromodeoxyuridine into the DNA of endometrial gland epithelial cells, and increased expression of estrogen receptor-alpha (ERalpha) and progesterone receptor in the luminal epithelium of the endometrium and subepithelial stroma. Because ERalpha is known to be expressed in these estrogen-target organs at the time of BPA exposure, it is plausible that BPA may directly affect the expression of ER-controlled genes involved in the morphogenesis of these organs. In addition, BPA-induced alterations that specifically affect hypothalamic-pituitary-gonadal axis function may further contribute to the anomalies observed at 3 mo of age, long after the cessation of BPA exposure.     

Bisphenol A induces permanent squamous change in mouse prostatic epithelium

Bisphenol A (BPA) is a monomer of plastic products widely used in daily life, and has weak estrogenic activity. In this study, male BALB/c mice were treated with BPA and diethylstilbestrol (DES) in adult and fetal periods to investigate whether BPA could affect prostatic epithelial differentiation. Eight-to 9-week-old mice treated for 3 weeks with subcutaneous implants of 0.2-200 mg BPA pellets induced the expression of cytokeratin 10 (CK10) in prostatic basal epithelial cells in a dose-dependent manner. Utilizing organ culture of adult prostate, 1 nM and 1 microM BPA also induced CK10 expression and squamous metaplasia with multilayering of basal epithelial cells, respectively. Fetal exposure to low-dose BPA (20 microg/kg/day) from gestation day (GD) 13 to GD18 induced permanent CK10 expression in basal cells of the adult prostate similar to DES (0.2 microg/kg/day). These results indicate that in mouse, BPA can directly elicit CK10 expression in prostatic epithelium, and that this change can be elicited by doses as low as 20 microg/kg/day. We speculate that low-dose BPA during fetal life may also induce permanent squamous change in human prostate.     

Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A

Hypothalamic neurons, which produce the kisspeptin family of peptide hormones (Kp), are critical for initiating puberty and maintaining estrous cyclicity by stimulating gonadotropin-releasing hormone (GnRH) release. Conversely, RFamide-related peptide-3 (RFRP3) neurons inhibit GnRH activity. It has previously been shown that neonatal exposure to bisphenol A (BPA) can alter the timing of female pubertal onset and induce irregular estrous cycles or premature anestrus. Here we tested the hypothesis that disrupted ontogeny of RFamide signaling pathways may be a mechanism underlying advanced puberty. To test this, we used a transgenic strain of Wistar rats whose GnRH neurons express enhanced green fluorescent protein. Pups were exposed by daily subcutaneous injection to vehicle, 17beta-estradiol (E2), 50 μg/kg BPA, or 50 mg/kg BPA, from Postnatal Day (PND) 0 through PND 3, and then cohorts were euthanized on PNDs 17, 21, 24, 28, and 33 (5-8 animals per age per exposure; males were collected on PNDs 21 and 33). Vaginal opening was advanced by E2 and 50 μg/kg BPA. On PND 28, females exposed to E2 and 50 μg/kg BPA had decreased RFRP-3 fiber density and contacts on GnRH neurons. RFRP3 perikarya were also decreased in females exposed to 50 μg/kg BPA. Data suggest that BPA-induced premature puberty results from decreased inhibition of GnRH neurons.     

Estrogenic Exposure Alters the Spermatogonial Stem Cells in the Developing Testis,Permanently Reducing Crossover Levels in the Adult

Bisphenol A (BPA) and other endocrine disrupting chemicals have been reported to induce negative effects on a wide range of physiological processes, including reproduction. In the female, BPA exposure increases meiotic errors, resulting in the production of chromosomally abnormal eggs. Although numerous studies have reported that estrogenic exposures negatively impact spermatogenesis, a direct link between exposures and meiotic errors in males has not been evaluated. To test the effect of estrogenic chemicals on meiotic chromosome dynamics, we exposed male mice to either BPA or to the strong synthetic estrogen, ethinyl estradiol during neonatal development when the first cells initiate meiosis. Although chromosome pairing and synapsis were unperturbed, exposed outbred CD-1 and inbred C3H/HeJ males had significantly reduced levels of crossovers, or meiotic recombination (as defined by the number of MLH1 foci in pachytene cells) by comparison with placebo. Unexpectedly, the effect was not limited to cells exposed at the time of meiotic entry but was evident in all subsequent waves of meiosis. To determine if the meiotic effects induced by estrogen result from changes to the soma or germline of the testis, we transplanted spermatogonial stem cells from exposed males into the testes of unexposed males. Reduced recombination was evident in meiocytes derived from colonies of transplanted cells. Taken together, our results suggest that brief exogenous estrogenic exposure causes subtle changes to the stem cell pool that result in permanent alterations in spermatogenesis (i.e., reduced recombination in descendent meiocytes) in the adult male.     

Early life exposure to endocrine-disrupting chemicals causes lifelong molecular reprogramming of the hypothalamus and premature reproductive aging

Gestational exposure to the estrogenic endocrine disruptor methoxychlor (MXC) disrupts the female reproductive system at the molecular, physiological, and behavioral levels in adulthood. The current study addressed whether perinatal exposure to endocrine disruptors re-programs expression of a suite of genes expressed in the hypothalamus that control reproductive function and related these molecular changes to premature reproductive aging. Fischer rats were exposed daily for 12 consecutive days to vehicle (dimethylsulfoxide), estradiol benzoate (EB) (1 mg/kg), and MXC (low dose, 20 μg/kg or high dose, 100 mg/kg), beginning on embryonic d 19 through postnatal d 7. The perinatally exposed females were aged to 16-17 months and monitored for reproductive senescence. After euthanasia, hypothalamic regions [preoptic area (POA) and medial basal hypothalamus] were dissected for real-time PCR of gene expression or pyrosequencing to assess DNA methylation of the Esr1 gene. Using a 48-gene PCR platform, two genes (Kiss1 and Esr1) were significantly different in the POA of endocrine-disrupting chemical-exposed rats compared with vehicle-exposed rats after Bonferroni correction. Fifteen POA genes were up-regulated by at least 50% in EB or high-dose MXC compared with vehicle. To understand the epigenetic basis of the increased Esr1 gene expression, we performed bisulfite conversion and pyrosequencing of the Esr1 promoter. EB-treated rats had significantly higher percentage of methylation at three CpG sites in the Esr1 promoter compared with control rats. Together with these molecular effects, perinatal MXC and EB altered estrous cyclicity and advanced reproductive senescence. Thus, early life exposure to endocrine disruptors has lifelong effects on neuroendocrine gene expression and DNA methylation, together with causing the advancement of reproductive senescence.     

Toxicity to early life stages and an estrogenic effect of a bisphenol A metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on the medaka (Oryzias latipes)

In a recent study, it was reported that 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a metabolite of bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane), showed estrogenic activity in several in vitro assays, and the estrogenic activity of MBP was higher than that of BPA. In this study, we have investigated the early life stage toxicity and estrogenic effect of MBP on medaka (Oryzias latipes). The 96-h median lethal concentration value of MBP and BPA with 24-h-old larvae was estimated to be 1,640 and 13,900 microg/l, respectively. The hatchability of fertilized eggs exposed to MBP and BPA over 14 days was significantly decreased at doses of 2,500 microg/l and 12,500 microg/l, respectively. Moreover, to compare the potency of estrogenic activity in vivo, male medaka were exposed to various concentrations of MBP and BPA for 21 days. The lowest-observed-effect concentrations of MBP and BPA for hepatic vitellogenin induction in male medaka were estimated to be 4.1 and 1,000 microg/l, respectively. These results suggest that MBP has high toxicity for early life stages of the medaka, and that the estrogenic activity of MBP was about 250-fold higher than that of BPA to male medaka.     

Food-associated estrogenic compounds induce estrogen receptor-mediated luciferase gene expression in transgenic male mice

The present paper aims at clarifying to what extent seven food-associated compounds, shown before to be estrogenic in vitro, can induce estrogenic effects in male mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc induction was determined in different tissues 8h after dosing the ER-luc male mice intraperitoneally (IP) or 14h after oral dosing. Estradiol-propionate (EP) was used as a positive control at 0.3 and 1mg/kg bodyweight (bw), DMSO as solvent control. The food-associated estrogenic compounds tested at non-toxic doses were bisphenol A (BPA) and nonylphenol (NP) (both at 10 and 50mg/kgbw), dichlorodiphenyldichloroethylene (p,p'-DDE; at 5 and 25mg/kgbw), quercetin (at 1.66 and 16.6mg/kgbw), di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 30 and 100mg/kgbw. In general IP dosing resulted in higher luc inductions than oral dosing. EP induced luc activity in the liver in a statistically significant dose-related way with the highest induction of all compounds tested which was 20,000 times higher than the induction by the DMSO-control. NP, DDE, DEHA and DIHP did not induce luc activity in any of the tissues tested. BPA induced luc in the liver up to 420 times via both exposure routes. BPA, DEHP and quercetin induced luc activity in the liver after oral exposure. BPA (50mg/kgbw IP) also induced luc activity in the testis, kidneys and tibia. The current study reveals that biomarker-responses in ER-luc male mice occur after a single oral exposure to food-associated estrogenic model compounds at exposure levels 10 to 10(4) times higher than the established TDI's for some of these compounds. Given the facts that (i) the present study did not include chronic exposure and that (ii) simultaneous exposure to multiple estrogenic compounds may be a realistic exposure scenario, it remains to be seen whether this margin is sufficiently high.     

Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse

Bisphenol A (BPA) is a synthetic monomer widely used to polymerize polycarbonate plastics and resins. It is shown in vitro to interfere with microtubules, producing aberations in mitotic and meiotic spindles. An increase of meiotic abnormalities in untreated female mice from an experimental colony was temporally correlated with the accidental release of BPA from polycarbonate cages and bottles damaged by inadvertent treatment with harsh alkaline detergents [P.A. Hunt, K.E. Koehler, M. Susiarjo, C.A. Hodges, A. Ilagan, R.C. Voigt, S. Thomas, B.F. Thomas, T.J. Hassold, Bisphenol A exposure causes meiotic aneuploidy in the female mouse, Curr. Biol. 13 (2003) 546-553]. In the present study, potential aneugenic effects of BPA on mouse male and female germ cells and bone marrow cells have been evaluated after acute, sub-chronic or chronic in vivo exposure. Female mice were orally treated with a single BPA dose, with 7 daily administrations or exposed for 7 weeks to BPA in drinking water. No significant induction of hyperploidy or polyploidy was observed in oocytes and zygotes at any treatment condition. The only detectable effect was a significant increase of metaphase II oocytes with prematurely separated chromatids after chronic exposure; this effect, however, had no irreversible consequence upon the fidelity of chromosome segregation during the second meiotic division, as demonstrated by the normal chromosome constitution of zygotes under the same exposure condition. With male mice, no delay of meiotic divisions was found after six daily oral doses of BPA with the BrdU assay. Similarly, no induction of hyperploidy and polyploidy was shown in epydidimal sperm hybrized with probes for chromosomes 8, X and Y, 22 days after six daily oral BPA doses. Finally, two daily oral BPA doses did not induce any increase of micronucleus frequencies in polychromatic erythrocytes of mouse bone marrow. In conclusion, our results do not add evidence to the suspected aneugenic activity of BPA and suggest that other factors or co-factors should be considered to explain the unexpected burst of meiotic abnormalities previously attributed to accidental BPA exposure.     

Bisphenol A exposure modifies DNA methylation of imprint genes in mouse fetal germ cells

Bisphenol A (BPA) is an estrogenic environmental toxin widely used for the production of plastics. Human frequent exposure to this chemical has been proposed to be a potential public health risk. The objective of this study was to assess the effects of BPA on DNA methylation of imprinting genes in fetal mouse germ cell. Pregnant mice were treated with BPA at doses of 0, 40, 80 and 160 μg BPA/kg body weight/day from 0.5 day post coitum. DNA methylation of imprinting genes, Igf2r, Peg3 and H19, was decreased with the increase of BPA concentration in fetal mouse germ cells (p < 0.01).The relative mRNA levels of Nobox were lower in BPA-treated group compared to control (BPA free) in female fetal germ cells, but in male fetal germ cells, a significant higher in Nobox expression was observed in BPA-treated group compared to control. Decreased mRNA expression of specific meiotic genes including Stimulated by Stra8 and Dazl were obtained in the female fetal germ cells. In conclusion, BPA exposure can affect the DNA methylation of imprinting genes in fetal mouse germ cells.     

Effect of LPS treatment on tyrosine hydroxylase expression and Parkinson-like behaviors

Puberty is a critical period of development during which the brain undergoes reorganizing and remodeling. Exposure to stress during this period is thought to interfere with normal brain development and increase susceptibility to mental illnesses. In female mice, pubertal exposure to lipopolysaccharide (LPS), a bacterial endotoxin, has been shown to alter sexual, anxiety-like, and depression-like behaviors and cognition in an enduring manner. However, the mechanisms underlying these effects remain unknown. The present study examined age and sex difference in tyrosine hydroxylase (TH) expression and dopamine-dependent and Parkinson-like behaviors following LPS treatment. The results show that LPS treatment during adulthood causes an enduring increase in TH expression in many of the brain regions examined. In contrast, there is no change in TH expression following LPS treatment during puberty. However, pubertal LPS treatment induces enduring behavioral deficits in tests of Parkinson-like behaviors, more so in male than in female mice. These results suggest that the low levels of TH following exposure to pubertal immune challenge may predispose mice to Parkinson-like behavior. These findings add to our understanding of stress and immune responses during puberty and their impact on mental health later in life.     

Inhibition of male chick phenotypes and spermatogenesis by Bisphenol-A

Bisphenol-A (BPA) has been reported to bind to the estrogen receptor (ER) and also to act as a xenoestrogen on the reproductive system of many species. In our previous study, a high dose of BPA disturbed the growth of the comb and testes of male chickens. In this study, the exposure of relatively low doses of BPA on the growth of the male chicken phenotypes was investigated. White Leghorn male chicks were orally administered various doses of BPA (2 microg to 200 mg/kg) from 2 weeks of age, and thereafter the comb, wattle and testes were examined at 5, 10, 15, 20 and 25 weeks of age. Although the body weight showed no significant difference among the birds of all ages, the growth of above organs was significantly affected in the chicks even with a minimal dose of 2-microg BPA. These inhibitory effects appeared in a dose-dependent manner. Histologically, the growth of the testes was negatively affected by exposure to over 20-microg/kg BPA: namely, the development of seminiferous tubuli and spermatogenesis were severely inhibited. The mRNA expressions of ERalpha and the aromatase gene (p450arom) increased in the testes in a dose-dependent manner after BPA administration. Accordingly, even low doses of BPA delayed the growth of the male chicken phenotype either by a direct effect or by an indirect response resulting in an increase in both of the endogenous estrogen levels and hyper-sensitivity to estrogen.     

Bisphenol a exposure causes meiotic aneuploidy in the female mouse

BACKGROUND: There is increasing concern that exposure to man-made substances that mimic endogenous hormones may adversely affect mammalian reproduction. Although a variety of reproductive complications have been ascribed to compounds with androgenic or estrogenic properties, little attention has been directed at the potential consequences of such exposures to the genetic quality of the gamete. RESULTS: A sudden, spontaneous increase in meiotic disturbances, including aneuploidy, in studies of oocytes from control female mice in our laboratory coincided with the accidental exposure of our animals to an environmental source of bisphenol A (BPA). BPA is an estrogenic compound widely used in the production of polycarbonate plastics and epoxy resins. We identified damaged caging material as the source of the exposure, as we were able to recapitulate the meiotic abnormalities by intentionally damaging cages and water bottles. In subsequent studies of female mice, we administered daily oral doses of BPA to directly test the hypothesis that low levels of BPA disrupt female meiosis. Our results demonstrated that the meiotic effects were dose dependent and could be induced by environmentally relevant doses of BPA. CONCLUSIONS: Both the initial inadvertent exposure and subsequent experimental studies suggest that BPA is a potent meiotic aneugen. Specifically, in the female mouse, short-term, low-dose exposure during the final stages of oocyte growth is sufficient to elicit detectable meiotic effects. These results provide the first unequivocal link between mammalian meiotic aneuploidy and an accidental environmental exposure and suggest that the oocyte and its meiotic spindle will provide a sensitive assay system for the study of reproductive toxins.     

Sex differences in behavioral and corticosterone responses to mild stressors in ICR mice are altered by ovariectomy in peripubertal period

Among rodents, females are generally considered to be highly responsive in terms of emotionality under stressful conditions, and have higher corticosterone levels and activity. In this study, we examined sex differences in mice by evaluating anxiety behaviors and corticosterone responses to mild stressors. In our first experiment, we analyzed the behavioral and corticosterone responses to the elevated plus-maze test and open-field test in male and female mice, and compared sex differences. Principal component analysis (PCA) was used to investigate the correlation of these responses between males and females. The corticosterone level was higher in females under both basal and stressed conditions. In the behavioral response, higher locomotor activity was seen in females in the elevated plus-maze test. PCA showed little association among anxiety behavior, locomotor activity, and corticosterone secretion. In our second experiment, we examined the activational effects of sex steroids on the corticosterone response to the elevated plus-maze test by gonadectomizing male and female mice and using testosterone or estrogen capsules as hormonal replacements. Sex differences at the basal corticosterone level were not altered by the hormonal milieu in adults, however the higher corticosterone level of females in response to stress was diminished by ovariectomy, although replacement with neither testosterone nor estrogen had any effect. These results suggest that the sex difference in novelty exposure observed in the form of a greater hypothalamic-pituitary-adrenal (HPA) axis response in female ICR mice is controlled by ovary-derived factors in adults.     

Pre- and postnatal bisphenol A treatment results in persistent deficits in the sexual behavior of male rats, but not female rats, in adulthood

Perinatal administration of the endocrine disruptor bisphenol A (BPA) reportedly inhibits the sexual behavior of sexually naïve adult male rats. In order to evaluate the effects of BPA administration during early development on later reproductive behavior, we administered one of five doses of bisphenol A daily to pregnant female rats throughout gestation and lactation, and quantified the appetitive and consummatory sexual behaviors of the resultant male and female offspring over multiple sexual encounters in adulthood. Males receiving low dose perinatal BPA (50 μg/kg bw/day) showed persistent deficits in sexual behavior in adulthood. Males receiving the highest dose (5 mg/kg bw/day), however, were indistinguishable from controls with respect to consummatory sexual behaviors but showed decreased latencies to engage in those behaviors when sexually naïve, with significant non-linear, or U-shaped, dose-response relationships observed on the first and last day of testing. Adult female sexual behavior was not affected by early BPA administration at any dose tested. These results are consistent with previous reports that BPA exerts behavioral effects especially at low doses, and further indicates that BPA can cause lasting impairment of sexual behavior in males, but does not alter the normal development of female appetitive or consummatory sexual behaviors. To our knowledge, this is the first report indicating that adult sexual performance is impaired in sexually experienced animals following perinatal exposure to bisphenol A.     

Behavioral despair in mice after prenatal stress

Maternal stress during pregnancy produced behavioral alterations in both sexes with regard to sexual behavior, aggressive, maternal, lateralization and depression. In the present paper, sex differences for depression in mice was studied. No sex differences between female and male mice groups were observed either in swimming-induced immobility or in the open-field test (ambulation, rearing and boluses). Prenatal stress produced: 1) an increase of immobility time in female mice for swimming-induced immobility, but not in male mice; 2) an increase of ambulation in female mice for open-field test, but not in male mice; 3) there were no significant differences in rearing and boluses between stress and control groups either for female or male mice. Prenatal stress increases the risk of depression and locomotor activity in adult female mice.