Prenatal BPA Exposure Research Articles

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes.

Bisphenols (BP), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and in rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal bisphenol exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal bisphenol exposure and postnatal maternal care on neurodevelopment and behavior in rats. Our findings suggest that the effects of prenatal bisphenol exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal bisphenol exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal bisphenol exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal bisphenol exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal bisphenol exposure and improve health and well-being in human populations.

Sex-specific impacts of prenatal bisphenol A exposure on genes associated with cortical development, social behaviors, and autism in the offspring’s prefrontal cortex

BackgroundRecent studies have shown that prenatal BPA exposure altered the transcriptome profiles of autism-related genes in the offspring’s hippocampus, disrupting hippocampal neuritogenesis and causing male-specific deficits in learning. However, the sex differences in the effects of prenatal BPA exposure on the developing prefrontal cortex, which is another brain region highly implicated in autism spectrum disorder (ASD), have not been investigated.MethodsWe obtained transcriptome data from RNA sequencing analysis of the prefrontal cortex of male and female rat pups prenatally exposed to BPA or control and reanalyzed. BPA-responsive genes associated with cortical development and social behaviors were selected for confirmation by qRT-PCR analysis. Neuritogenesis of primary cells from the prefrontal cortex of pups prenatally exposed to BPA or control was examined. The social behaviors of the pups were assessed using the two-trial and three-chamber tests. The male-specific impact of the downregulation of a selected BPA-responsive gene (i.e., Sema5a) on cortical development in vivo was interrogated using siRNA-mediated knockdown by an in utero electroporation technique.ResultsGenes disrupted by prenatal BPA exposure were associated with ASD and showed sex-specific dysregulation. Sema5a and Slc9a9, which were involved in neuritogenesis and social behaviors, were downregulated only in males, while Anxa2 and Junb, which were also linked to neuritogenesis and social behaviors, were suppressed only in females. Neuritogenesis was increased in males and showed a strong inverse correlation with Sema5a and Slc9a9 expression levels, whereas, in the females, neuritogenesis was decreased and correlated with Anxa2 and Junb levels. The siRNA-mediated knockdown of Sema5a in males also impaired cortical development in utero. Consistent with Anxa2 and Junb downregulations, deficits in social novelty were observed only in female offspring but not in males.ConclusionThis is the first study to show that prenatal BPA exposure dysregulated the expression of ASD-related genes and functions, including cortical neuritogenesis and development and social behaviors, in a sex-dependent manner. Our findings suggest that, besides the hippocampus, BPA could also exert its adverse effects through sex-specific molecular mechanisms in the offspring’s prefrontal cortex, which in turn would lead to sex differences in ASD-related neuropathology and clinical manifestations, which deserves further investigation.

Prenatal BPA exposure disrupts male reproductive functions by interfering with DNA methylation and GDNF expression in the testes of male offspring rats.

BPA is a ubiquitous environmental endocrine-disrupting chemical, and maternal exposure to BPA is associated with impaired male reproductive functions; however, the mechanisms remain to be elucidated. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in maintaining normal spermatogenesis and fertility. However, the effect of prenatal BPA exposure on GDNF expression and its mechanism in the testis has not been reported. In this study, pregnant Sprague-Dawley rats were respectively exposed to 0, 0.05, 0.5, 5, and 50 mg/kg/day BPA via oral gavage from gestational day (GD) 5 to GD 19, with 6 pregnant rats in each group. ELISA, histochemistry, real-time PCR, western blot, and methylation-specific PCR (MSP) were used to detect the sex hormone levels, testicular histopathology, mRNA and protein expression of DNA methyltransferases (DNMTs) and GDNF, and the promoter methylation of Gdnf in the testes of male offspring at postnatal day (PND) 21 and PND 56. Prenatal BPA exposure increased body weight; decreased sperm counts and serum levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH); and induced testicular histological damage, which indicated the damage of male reproductive function. Prenatal BPA exposure also upregulated Dnmt1 in 5 mg/kg group and Dnmt3b in 0.5 mg/kg group, but down-regulated Dnmt1 in 50 mg/kg group at PND 21. At PND 56, Dnmt1 was significantly increased in 0.05 mg/kg group but decreased in 0.5, 5, and 50 mg/kg groups, Dnmt3a was decreased, and Dnmt3b was markedly increased in 0.05 and 0.5 mg/kg groups but decreased in 5 and 50 mg/kg groups. The mRNA and protein expression levels of Gdnf were decreased markedly in 0.5 and 50 mg/kg groups at PND 21. And the methylation level of Gdnf promoter was significantly increased in 0.5 mg/kg group, but decreased in 5 and 50 mg/kg groups at PND 21. In conclusion, our study indicates that prenatal BPA exposure disrupts male reproductive functions, interferes with the expression of DNMTs, and decreases Gdnf expression in the testes of male offspring. Gdnf expression may be regulated by DNA methylation; however, the detailed mechanism needs to be further investigated.

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A, F, and S in 6-Year-old Children in Korea.

ObjectivesBisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children.MethodsPrenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T3, and free T4) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations.ResultsThe associations between prenatal BPA and total T3 levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T4 levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only.ConclusionsOur findings identified significant associations between prenatal BPA exposure and total T3 levels in all children and between BPF exposure and free T4 levels in girls only.

The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model

This study aimed to examine the impact of BPA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRNAs (miRNAs) related to heart development and diseases. Pregnancy is known to be the “critical windows” in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BPA. BPA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRNAs expression in cardiac of mother- and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p < 0.05). Interestingly, significant changes in systolic and diastolic blood pressure between the first and third trimester of BPA-exposed pregnant rats were also observed (p < 0.05). In BPA-exposed pregnant rats, miR-499-5p was significantly altered in the heart (p < 0.01). Meanwhile, altered miR-17-5p, -208-3p, and -210-3p expressions were observed in all heart of the foetuses from BPA-exposed pregnant rats (p < 0.05). In H&E staining, BPA-exposed foetal hearts showed a sign of fibrosis while BPA-exposed pregnant rats showed muscle remnant. Masson trichrome staining further confirmed the presence of fibrosis observed in BPA-exposed foetal heart and reduced expression of cardiac troponin I (cTnI) was also observed in BPA-exposed foetal heart. In summary, altered cardiac miRNAs with histological changes were observed in both mother- and foetus-exposed BPA These findings put forward the importance of future work to further understand how prenatal BPA exposure affect foetuses in their later stage of life.

Prenatal Bisphenol A exposure and early childhood neurodevelopment in Shandong, China.

Several epidemiological studies suggest that prenatal exposure to BPA may interfere with the neurodevelopment of pre-school and school-age children. However, a limited number of studies are available for effects during children at a younger age, especially in China. Based on Laizhou Wan Birth Cohort (LWBC), BPA concentrations were measured in urine among 506 pregnant women during their hospital admission for delivery and neurodevelopment of their children was assessed using the Gesell Development Schedules at 12 months (n = 368) and 24 months (n = 296). Linear regression and generalized linear models were used to analyze the association between prenatal BPA exposure and the children's developmental quotient scores (DQs). The median of maternal BPA concentration was 0.48 μg/L or 1.05 μg/g creatinine. Maternal BPA concentrations were adversely associated with children DQs at 12 months of age, with a 10-fold increase in prenatal BPA concentrations correlated to 1.43-point decrease in DQs in the adaptive domain (β = -1.43; 95% CI: -2.30 to -0.56, p = 0.001). When stratified by gender, prenatal BPA concentrations were adversely associated with the adaptive domain DQs among boys (p-trend = 0.012) and girls (p-trend = 0.028) and the social domain DQs (p-trend = 0.019) only among girls. At 24 months of age, the significant adverse association was only found in the language domain among girls (β = -1.69; 95% CI: -3.23 to -0.15, p = 0.032). Based on a Chinese population, we found potential impacts of prenatal BPA exposure on childhood neurodevelopment at 12 and 24 months of age, especially among girls.

Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep.

Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017. © 2016 Wiley Periodicals, Inc.

Associated prenatal factors of behavioral and emotional problems in 5 year-old children: The Hokkaido Study

Introduction: Prenatal environment is considered to contribute childhood development and behavior. The aim of this study was to evaluate prenatal environmental factors including chemical exposures and socio-economic status which were associated with increased risk of child behavioral and emotional difficulties. Methods: 3813 Japanese version of parent report Strength and Difficulty Questionnaire (SDQ) were distributed to the subpopulation of prospective birth cohort study as a follow-up study at 5 year of age between Oct. 2014 and Dec, 2015. Total difficulties score (TDS) and scores of five subscales were examined. Maternal smoking, drinking and BMI, parental age, education, family income were obtained from baseline questionnaire. Birth weight, infant sex and gestational age were obtained from birth record. Maternal BPA and phthalates levels were measured to assess prenatal exposure to environmental chemicals. Results: The response rate was 67.1%. 2553 valid response were included into the analysis. The mean TDS was 8.73 ± 5.06 and boys showed significantly higher TDS compared to girls (P &lt; 0.001). 20.4% (N=284) of children were above cut-off (TDS ≧ 13). Factors that increased the risk of having overall behavioral and emotional difficulties were; lower parental education levels, younger parental age, lower family income, higher maternal BMI, maternal smoking, being a boy and first child. Especially family income was strong contributing factor of each subscale except prosocial behavior. Maternal drinking, birth weight and gestational age were not associated. Maternal BPA level was significantly higher among children above TDS cut-off value (P = 0.012). Phthalate levels were no significantly different. Conclusion: This study found significant contributing factors of increased risk of child behavioral and emotional difficulties. Prenatal BPA exposure may be associated with behavioral and emotional problems in 5 year-old children.

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

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

Impact of gestational bisphenol A on oxidative stress and free fatty acids: Human association and interspecies animal testing studies.

Bisphenol A (BPA) is a high production volume chemical and an endocrine disruptor. Developmental exposures to BPA have been linked to adult metabolic pathologies, but the pathways through which these disruptions occur remain unknown. This is a comprehensive interspecies association vs causal study to evaluate risks posed by prenatal BPA exposure and to facilitate discovery of biomarkers of relevance to BPA toxicity. Samples from human pregnancies during the first trimester and at term, as well as fetal and/or adult samples from prenatally BPA-treated sheep, rats, and mice, were collected to assess the impact of BPA on free fatty acid and oxidative stress dynamics. Mothers exposed to higher BPA during early to midpregnancy and their matching term cord samples displayed increased 3-nitrotyrosine (NY), a marker of nitrosative stress. Maternal samples had increased palmitic acid, which was positively correlated with NY. Sheep fetuses and adult sheep and rats prenatally exposed to a human-relevant exposure dose of BPA showed increased systemic nitrosative stress. The strongest effect of BPA on circulating free fatty acids was observed in adult mice in the absence of increased oxidative stress. This is the first multispecies study that combines human association and animal causal studies assessing the risk posed by prenatal BPA exposure to metabolic health. This study provides evidence of the induction of nitrosative stress by prenatal BPA in both the mother and fetus at time of birth and is thus supportive of the use of maternal NY as a biomarker for offspring health.

Potential Role for IFNγ in Promoting Asthma After Prenatal Exposure to BPA

We have reported that prenatal BPA exposure promotes the development of allergic asthma in a mouse model. This study was designed to identify the immune mechanism(s) by which BPA exposure enhances asthma in early life.

Prenatal exposure to bisphenol A and phthalates and infant neurobehavior

Objective To examine the association of prenatal exposure to bisphenol A and select common phthalates with infant neurobehavior measured at 5 weeks. Methods We compared the concentration of maternal urinary metabolites of bisphenol A and phthalates at two distinct time points in pregnancy (16w, 26w) with scores on the NICU Network Neurobehavioral Scale (NNNS) at 5 weeks of age in a cohort of 350 mother/infant pairs. Results Prenatal exposure to BPA was not significantly associated with neurobehavioral outcomes at 5 weeks. Significant associations between prenatal exposure to measured phthalates and infant neurobehavioral outcomes differed by type of phthalate and were only seen with exposure measured at 26 weeks. Higher total di-butyl phthalate (DBP) metabolites at 26w were associated with improved behavioral organization evidenced by decreased arousal (p = .04), increased self-regulation (p = .052), and decreased handling (p = .02). In males, higher total di-2-ethylhexyl phthalate (DEHP) metabolites at 26w were associated with more nonoptimal reflexes (p = .02). Conclusion The association between prenatal phthalate exposure and infant neurobehavior differed by type of phthalate and was evident only with exposure measured at 26w. Prenatal exposure to DBP was associated with improved behavioral organization in 5-week-old infants. Prenatal exposure to DEHP was associated with nonoptimal reflexes in male infants. There was no evidence of an association between prenatal BPA exposure and infant neurobehavior.

Prenatal exposure to bisphenol A promotes angiogenesis and alters steroid-mediated responses in the mammary glands of cycling rats

Prenatal exposure to BPA disturbs mammary gland histoarchitecture and increases the carcinogenic susceptibility to chemical challenges administered long after BPA exposure. Our aim was to assess the effect of prenatal BPA exposure on mammary gland angiogenesis and steroid hormone pathways in virgin cycling rats. Pregnant Wistar rats were exposed to either 25 or 250μg/kg/day (25 and 250 BPA, respectively) or to vehicle. Female offspring were autopsied on postnatal day (PND) 50 or 110. Ovarian steroid serum levels, the expression of steroid receptors and their co-regulators SRC-3 and SMRT in the mammary gland, and angiogenesis were evaluated. At PND 50, all BPA-treated animals had lower serum levels of progesterone, while estradiol levels remained unchanged. The higher dose of BPA increased mammary ERα and decreased SRC-3 expression at PND 50 and PND 110. SMRT protein levels were similar among groups at PND 50, whereas at PND 110, animals exposed to 250 BPA showed a lower SMRT expression. Interestingly, in the control and 25 BPA groups, SMRT increased from PND 50 to PND 110. At PND 50, an increased vascular area associated with higher VEGF expression was observed in the 250 BPA-treated rats. At PND 110, the vascular area was still increased, but VEGF expression was similar to that of control rats. The present results demonstrate that prenatal exposure to BPA alters the endocrine environment of the mammary gland and its angiogenic process. Increased angiogenesis and altered steroid hormone signals could explain the higher frequency of pre-neoplastic lesions found later in life.This article is part of a Special Issue entitled ‘Endocrine disruptors’.

Effects of Prenatal Bisphenol-A on Goal-Directed Behavior and Insulin Resistance in Suffolk Sheep

Event Abstract Back to Event Effects of Prenatal Bisphenol-A on Goal-Directed Behavior and Insulin Resistance in Suffolk Sheep Nesha R. Jairam1*, Elizabeth M. Peckham2, Vasantha Padmanabhan3 and Theresa M. Lee1, 2 1 University of Michigan, Psychology Graduate Program, Biopsychology, United States 2 University of Michigan, Neuroscience Program, United States 3 University of Michigan, Department of Pediatrics & Molecular and Integrative Physiology, United States Bisphenol-A, an endocrine disrupting chemical that mimics estrogen, is found in commonly used containers. Low doses of exposure in human fetuses are of concern during periods of development. Previous research shows that prenatal BPA exposure elevated the risk of insulin resistance in mice; this current study investigates whether insulin responses are predictive of behavioral responses in tests of goal-directed behaviors in a sheep model. Goal-directed behavior was determined by measuring consumption of palatable food (PFT) and the rate of learning in a conditioned place preference test (CPP), in male and female peripubertal animals exposed to 0.5 mg/kg/day BPA or vehicle daily between days 30-90G. Insulin responses were determined using a glucose tolerance test. Control males demonstrated greater goal directed behavior for food than control females. BPA and control males show no difference in the amount of food consumed in the PFT. BPA females and injection controls (IC) are consuming more food than uninjected control females, 89.77% and 86.09% respectively, which was significantly higher than uninjected control females (57.77%). BPA males and BPA females show no difference in time spent in the conditioned side of a CPP from same-sex controls. There is no effect of BPA on male motivation for food. In females, daily injection of the ewe has masculinized the motivation for food. This study demonstrates the sex differences in food-induced goal directed behavior is not affected by BPA doses commonly found in humans. Acknowledgements NIEHS Grant: R01 ES019189 Reproductive Sciences Program Lee Neuroendocrinology Lab Padmanabhan Lab Stephanie Stout – Lab Technician Alexander Kastl – Lab Technician Celia Upton, Kate Gilliam, and Emily Sheppard References Alonso-Magdalena, P., Vieira, E., Soriano, S., Menes, L., Burks, D., Quesada, I., et al. (2010). Bisphenol A exposure during Pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environmental Health Perspectives, 118(9), 1243-1250. Maffini, M. V., Rubin, B. S., Sonnenschein, C., & Soto, A. M. (2006). Endocrine disruptors and reproductive health: The case of bisphenol-A. Molecular and Cellular Endocrinology, 254, 179-186. Keywords: Behavior, Bisphenol-A, goal-directed, Hormones, Insulin Resistance, prenatal Conference: NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology, Ann Arbor, United States, 13 Jul - 16 Jul, 2011. Presentation Type: Poster Topic: Environmental endocrinology Citation: Jairam NR, Peckham EM, Padmanabhan V and Lee TM (2011). Effects of Prenatal Bisphenol-A on Goal-Directed Behavior and Insulin Resistance in Suffolk Sheep. Front. Endocrinol. Conference Abstract: NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology. doi: 10.3389/conf.fendo.2011.04.00146 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jul 2011; Published Online: 09 Aug 2011. * Correspondence: Miss. Nesha R Jairam, University of Michigan, Psychology Graduate Program, Biopsychology, Ann Arbor, MI, 48109, United States, reddica@umich.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nesha R Jairam Elizabeth M Peckham Vasantha Padmanabhan Theresa M Lee Google Nesha R Jairam Elizabeth M Peckham Vasantha Padmanabhan Theresa M Lee Google Scholar Nesha R Jairam Elizabeth M Peckham Vasantha Padmanabhan Theresa M Lee PubMed Nesha R Jairam Elizabeth M Peckham Vasantha Padmanabhan Theresa M Lee Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Exposure to Bisphenol A Prenatally or in Adulthood Promotes T H 2 Cytokine Production Associated with Reduction of CD4 + CD25 + Regulatory T Cells

BackgroundBisphenol A (BPA) is a widespread endocrine-disrupting chemical that can affect humans and animals.ObjectivesWe investigated the effects of adult or prenatal exposure to BPA on T-helper (TH)1/TH2 immune responses and the mechanisms underlying these effects.MethodsTo evaluate the effects of exposure to BPA in adulthood, male Leishmania major–susceptible BALB/c and –resistant C57BL/6 mice were subcutaneously injected with 0.625, 1.25, 2.5, and 5 μmol BPA 1 week before being infected with L. major. To evaluate prenatal exposure, female mice were given BPA-containing drinking water at concentrations of 1, 10, and 100 nM for 2 weeks, then mated, and given BPA for another week. Male 10-week-old offspring were infected with L. major. Footpad swelling was assessed as a measure of the course of infection.ResultsMice exposed to BPA prenatally or in adulthood showed a dose-dependent increase in footpad swelling after being infected with L. major. Exposure to BPA in adulthood significantly promoted antigen-stimulated production of interleukin (IL)-4, IL-10, and IL-13 but not interferon-γ (IFN-γ). However, mice prenatally exposed to BPA showed increased production of not only IL-4 but also IFN-γ. The percentages of CD4+CD25+ cells were decreased in mice exposed to BPA either prenatally or in adulthood. Effects of prenatal BPA exposure were far more pronounced than effects of exposure in adulthood.ConclusionBPA promotes the development of TH2 cells in adulthood and both TH1 and TH2 cells in prenatal stages by reducing the number of regulatory T cells.