Maternal Bisphenol Research Articles

Maternal bisphenol A (BPA) exposure induces placental dysfunction and health risk in adult female offspring: Insights from a mouse model

Bisphenol A (BPA) is an endocrine disruptor that poses multiple risks to human health. In particular, the potential adverse effects of maternal exposure to BPA on offspring warrant further investigation. In this study, pregnant mice were exposed to BPA throughout gestation and the effects of BPA on placental function, fetal development, and health risks in adult offspring were assessed. The results showed that exposure to BPA during pregnancy led to abnormal fetal weight during the mid-to-late stages. Positron emission tomography (PET)/computed tomography (CT) and quantitative polymerase chain reaction (qPCR) were used to assess the expression of glucose transporters. The results showed that maternal BPA exposure altered glucose transport by upregulating Glut1. This alteration may significantly affect placental function and fetal development. Placental metabolomic analysis showed that BPA exposure led to downregulation of key intermediates in glucose metabolism, including UDP-d-glucose and D-glucosamine-6-phosphate. Additionally, the glycerophospholipid metabolite Dipalmitoylphosphatidylcholine (DPPC) was upregulated while CDP-choline and CDP-ethanolamine were downregulated. These disturbances in placental energy metabolism and alterations in glucose transport may be related to decreased fasting blood glucose levels and abnormal glucose tolerance in female offspring; however, these indices remained unaltered in male offspring. These findings provide preliminary insights into the potential pathological mechanisms underlying placental dysfunction and health risk caused by maternal BPA exposure in adult female offspring.

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Fetal Origin of Abnormal Glucose Tolerance in Adult Offspring Induced by Maternal Bisphenol A Analogs Exposure.

With the widespread use of bisphenol A (BPA) analogs, their health risks have attracted attention. The effects of maternal BPA analogs exposure on glucose homeostasis in adult offspring and the underlying fetal origins require further exploration. Herein, we exposed pregnant mice to two types of BPA analogs─BPB and BPAF; we evaluated glucose homeostasis in adult offspring and maternal-fetal glucose transport by testing intraperitoneal glucose tolerance, determining glucose and glycogen contents, conducting positron emission tomography (PET)/computed tomography (CT), detecting expression of placental nutrient transport factors, and assessing placental barrier status. We observed that adult female offspring maternally exposed to BPB and BPAF exhibited low fasting blood glucose in adulthood, with even abnormal glucose tolerance in the BPAF group. This phenomenon can be traced back to the elevated fetal glucose induced by the increased efficiency of placenta glucose transport in late pregnancy. On the other hand, the expression of genes associated with vascular development and glucose transport was significantly altered in the placenta in the BPAF group, potentially contributing to enhanced fetal glucose. These findings provide preliminary insights into potential mechanisms underlying the disturbance of glucose metabolism in adult female offspring mice induced by maternal exposure to BPA analogs.

Neurodevelopmental effects of prenatal Bisphenol A exposure on the role of microRNA regulating NMDA receptor subunits in the male rat hippocampus

Maternal bisphenol A (BPA) exposure has been reported to cause learning and memory deficits in born offspring. However, little is known that this impairment is potentially caused by epigenetic modulation on the development of NMDA receptor subunits. This study investigates the effect of prenatal BPA exposure on the hippocampal miR-19a and miR-539, which are responsible for regulating NMDA receptor subunits as well as learning and memory functions. Pregnant Sprague Dawley rats were orally administered with 5 mg/kg/day of BPA from pregnancy day 1 (PD1) until gestation day 21 (GD21), while control mothers received no BPA. The mothers were observed daily until GD21 for either a cesarean section or spontaneous delivery. The male offspring were sacrificed when reaching GD21 (fetus), postnatal days 7, 14, 21 (PND7, 14, 21) and adolescent age 35 (AD35) where their hippocampi were dissected from the brain. The expression of targeted miR-19a, miR-539, GRIN2A, and GRIN2B were determined by qRT-PCR while the level of GluN2A and GluN2B were estimated by western blot. At AD35, the rats were assessed with neurobehavioral tests to evaluate their learning and memory function. The findings showed that prenatal BPA exposure at 5 mg/kg/day significantly reduces the expression of miR-19a, miR-539, GRIN2A, and GRIN2B genes in the male rat hippocampus at all ages. The level of GluN2A and GluN2B proteins is also significantly reduced when reaching adolescent age. Consequently, the rats showed spatial and fear memory impairments when reaching AD35. In conclusion, prenatal BPA exposure disrupts the role of miR-19a and miR-539 in regulating the NMDA receptor subunit in the hippocampus which may be one of the causes of memory and learning impairment in adolescent rats.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to twoyears and to identify the critical exposure periods. A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first twoyears, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033kb).

Maternal Bisphenol a Levels in Patients Diagnosed with Preeclampsia: A Case-Control Study

Objective: This study aims to assess Bisphenol-A levels in serum samples from preeclampsia patients and determine potential distinctions by comparing them against samples from healthy pregnant women
 Material-Methods: This single-center prospective case-control study aimed to investigate the potential differences in serum Bisphenol-A (BPA) levels between pregnant patients diagnosed with preeclampsia and healthy pregnant women. The study encompassed two distinct groups: the study group consisted of 30 pregnant patients diagnosed with preeclampsia, while the control group included 30 healthy pregnant women matched in terms of gestational weeks and demographic characteristics, maintaining a 1:1 ratio. Serum samples were subjected to analysis using a BPA ELISA kit
 Results: The study encompassed a total of 60 patients, who were categorized into two groups: preeclampsia (n=30) and control (n=30). Upon comparison of the BPA values between the two groups, no statistically significant difference was detected (p=0.579).
 Conclusion: Clear-cut scientific evidence establishing a conclusive causal link between BPA and preeclampsia is still lacking. Further research is needed in this area

Prenatal bisphenol exposure and intelligence quotient in children at six years of age: A prospective cohort study

The effects of prenatal bisphenol A (BPA) exposure on children's cognitive development have been reported; however, relevant evidence on BPA analogues was limited, with rare evidence of the joint effect of their mixture. Among 424 mother-offspring pairs from the Shanghai-Minhang Birth Cohort Study, maternal urinary concentrations of five bisphenols (BPs) were quantified, and children's cognitive function was assessed by the Wechsler Intelligence Scale at six years of age. We assessed the associations of prenatal exposure to individual BPs with children's intelligence quotient (IQ) and analyzed the joint effect of BPs mixture by the Quantile g-computation model (QGC) and Bayesian kernel machine regression model (BKMR). QGC models showed that higher maternal urinary BPs mixture concentrations were associated with lower scores among boys in a non-linear way; however, no association was observed in girls. For individual effects, BPA and BPF were associated with decreased IQ scores in boys and were identified as important contributors to the joint effect of BPs mixture. However, associations of BPA with increased IQ scores in girls, and TCBPA with increased IQ scores in both sexes were observed. Our findings suggested prenatal exposure to BPs mixture may affect children's cognitive function in a sex-specific pattern and provided evidence of the neurotoxicity of BPA and BPF.

Multigenerational effect of maternal bisphenol A exposure on DNA methylation in F1 sperm

Multigenerational effect of maternal bisphenol A exposure on DNA methylation in F1 sperm

Associations of bisphenol exposure with thyroid hormones in pregnant women: a prospective birth cohort study in China.

Bisphenols are endocrine disruptor chemicals that disrupt thyroid hormone homeostasis. However, evidence on the effects of bisphenol mixtures on thyroid hormones are insufficient. Therefore, the present study aimed to explore the effects of bisphenol substitutes and bisphenol mixtures on thyroid hormones during pregnancy. The study was conducted among 446 pregnant women in the Guangxi Zhuang Birth Cohort (GZBC), China. In multiple linear regressions, compared with the low-exposure group, bisphenol S (BPS) concentrations in the middle-exposure group led to a 10.90% (95% CI: - 18.16%, - 2.99%) decrease in triiodothyronine (T3) levels in the first trimester; tetrabromobisphenol A (TBBPA) levels in the middle-exposure group led to an 8.26% (95% CI: - 15.82%, - 0.01%) decrease in T3 levels in the first trimester; bisphenol B (BPB) levels in the middle-exposure group led to higher free thyroxine (FT4) levels (9.84%; 95% CI: 1.73%, 18.60%) in the second trimester; bisphenol F (BPF) in the middle-exposure group led to higher FT4 levels (8.59%, 95% CI: 0.53%, 17.31%) in the second trimester; and TBBPA levels in the high-exposure group led to a 9.39% (95% CI: 1.46%, 17.93%) increase in FT4 levels in the second trimester. The Bayesian kernel machine regression (BKMR) and restricted cubic spline (RCS) models showed a U-shaped dose-response relationship between bisphenol A (BPA) and free triiodothyronine (FT3) (p < 0.01) as well as BPS and FT4 (p < 0.05). Nonlinear relationships were also observed between the bisphenol mixture and FT3. Overall, maternal bisphenol exposure affected thyroid hormone levels during pregnancy. This study provides evidence that BPB, BPF, BPS, and TBBPA are unsafe substitutes for BPA, as well as the overall effect of bisphenols on adverse health in human beings.

Maternal bisphenol A and triclosan exposure and allergic diseases in childhood: a meta-analysis of cohort studies.

Bisphenol A (BPA) and triclosan (TCS) are both endocrine-disrupting chemicals (EDCs), and pregnant women are usually exposed to them through daily consumption. This study aimed to explore the relationship between prenatal BPA and TCS exposure and allergic diseases in childhood by systematic review and meta-analysis. We searched the topic of prenatal BPA and TCS exposure and allergic diseases in childhood published before March 22, 2021, in four databases, including PubMed, Web of Science, Embase, and Cochrane. Statistical analysis was completed using Stata software (version 16.0). Seven papers on BPA and four papers on TCS were included in this meta-analysis. The association between prenatal exposure to BPA and total allergic diseases in childhood showed a pooled effect estimate of 1.13 (95% CI, 1.04, 1.23), with I2 = 0.0% (P = 0.615). The effect estimates between BPA exposure and each allergic disease were 1.18 (95% CI, 1.02, 1.36) for wheezing, 1.23 (95% CI, 1.01, 1.50) for asthma, 1.03 (95% CI, 0.89, 1.18) for eczema/rashes or hives, and 1.19 (95% CI, 0.91, 1.56) for aeroallergies. Prenatal exposure to TCS had no association with the four types of allergic disease in childhood. BPA exposure during the prenatal period was positively associated with allergic disease in childhood. Strengthening prenatal EDC exposure control is necessary for child health.

Alteration of Extracellular Matrix Components in the Anterior Pituitary Gland of Neonatal Rats Induced by a Maternal Bisphenol A Diet during Pregnancy.

The extracellular matrix (ECM) plays crucial roles in the anterior pituitary gland via the mechanism of cell–ECM interaction. Since bisphenol A (BPA), a well-known endocrine disruptor, can cross through the placenta from mother to fetus and bind with estrogen receptors, cell populations in the neonatal anterior pituitary gland could be the target cells affected by this chemical. The present study treated maternal rats with 5000 µg/kg body weight of BPA daily throughout the pregnancy period and then investigated the changes in ECM-producing cells, i.e., pericytes and folliculostellate (FS) cells, including their ECM production in the neonatal anterior pituitary at Day 1. We found that pericytes and their collagen synthesis reduced, consistent with the increase in the number of FS cells that expressed several ECM regulators—matrix metalloproteinase (MMP) 9 and the tissue inhibitors of metalloproteinase (TIMP) family. The relative MMP9/TIMP1 ratio was extremely high, indicating that the control of ECM homeostasis was unbalanced. Moreover, transmission electron microscopy showed the unorganized cell cluster in the BPA-treated group. This study revealed that although the mother received BPA at the “no observed adverse effect” level, alterations in ECM-producing cells as well as collagen and the related ECM balancing genes occurred in the neonatal anterior pituitary gland.

Associations of maternal bisphenol urine concentrations during pregnancy with neonatal metabolomic profiles

BackgroundFetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood.MethodsIn a population-based prospective cohort study among 225 mother–child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC–MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood.ResultsNo associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics.DiscussionHigher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.

Maternal Bisphenol A (BPA) Exposure Alters Cerebral Cortical Morphogenesis and Synaptic Function in Mice.

Early-life exposure to bisphenol A (BPA), synthetic compound used in polycarbonate plastic, is associated with altered cognitive and emotional behavior later in life. However, the brain mechanism underlying the behavioral deficits is unknown. Here, we show that maternal BPA exposure disrupted self-renewal and differentiation of neural progenitors during cortical development. The BPA exposure reduced the neuron number, whereas it increased glial cells in the cerebral cortex. Also, synaptic formation and transmission in the cerebral cortex were suppressed after maternal BPA exposure. These changes appeared to be associated with autophagy as a gene ontology analysis of RNA-seq identified an autophagy domain in the BPA condition. Mouse behavioral tests revealed that maternal BPA caused hyperactivity and social deficits in adult offspring. Together, these results suggest that maternal BPA exposure leads to abnormal cortical architecture and function likely by activating autophagy.

Maternal bisphenol urine concentrations, fetal growth and adverse birth outcomes: A population-based prospective cohort

BackgroundExposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods.MethodsIn a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth.ResultsAn interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth.ConclusionsHigher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

Bisphenol A and S in the Urine of Newborns: Plastic for Non-Food Use Still without Rules.

The aim of the present study was to assess the effects of bisphenol (BP) exposure on pregnancy and neonatal life. We have (a) determined BP (BPA and BPS) concentration levels in a group of newborns and their mothers; (b) identified factors, habits, and devices possibly responsible for BP uptake; and (c) determined the effect of BP exposure. No significant correlations were detected between maternal and neonatal BP concentration levels. In newborns, positive correlations between pacifier use and BPS total (p = 0.04) and free BPS (p = 0.03) concentrations were detected. A significant correlation was also found between oral glucose administration and concentration levels of free BPA (p < 0.05). Our study points to a central role of lifestyle, hospital procedures, and neonatal devices in inducing BP exposure, especially during the perinatal period. This is the first report of BP contamination in newborns due to widely non-alimentary products designed for newborn care, such as glucose-solution containers for BPA and pacifiers for BPS. Further studies are advocated in order to clarify both the impact of other BP forms on human health and development, as well as potential BPA exposure sources during neonatal and childhood life.

Fetal exposure to phthalates and bisphenols and childhood general and organ fat. A population-based prospective cohort study.

Fetal exposure to phthalates and bisphenols might have long-lasting effects on growth and fat development. Not much is known about the effects on general and organ fat development in childhood. We assessed the associations of fetal exposure to phthalates and bisphenols with general and organ fat measures in school-aged children. In a population-based, prospective cohort study among 1128 mother-child pairs, we measured maternal urinary phthalate metabolites and bisphenol concentrations in first, second, and third trimester. Offspring body mass index, fat mass index by dual-energy X-ray absorptiometry, and visceral and pericardial fat indices and liver fat fraction were measured by magnetic resonance imaging at 10 years. After adjustment for confounders and correction for multiple testing, an interquartile range increase in first trimester phthalic acid concentrations remained associated with a 0.14 (95% confidence interval: 0.05, 0.22) standard deviation score increase in pericardial fat index. We also observed tendencies for associations of higher maternal low molecular weight phthalate urinary concentrations in second trimester with childhood pericardial fat index, but these were not significant after adjustment for multiple testing. High molecular weight phthalate, di-2-ethylhexyl phthalate, and di-n-octyl phthalate concentrations were not associated with childhood outcomes. Maternal urinary bisphenol concentrations were not associated with childhood adiposity. Maternal first trimester phthalic acid concentrations are associated with increased childhood pericardial fat index at 10 years of age, whereas maternal bisphenol concentrations are not associated with childhood adiposity. We did not find significant sex-specific effects. These findings should be considered as hypothesis generating and need further replication and identification of underlying mechanisms.

Fetal phthalates and bisphenols and childhood lipid and glucose metabolism. A population-based prospective cohort study

Background and aimsFetal exposure to endocrine disruptors such as phthalates and bisphenols may lead to developmental metabolic adaptations. We examined associations of maternal phthalate and bisphenol urine concentrations during pregnancy with lipids, insulin, and glucose concentrations at school age. MethodsIn a population-based, prospective cohort study among 757 mother–child pairs, we measured maternal phthalate and bisphenol urine concentrations in first, second and third trimester of pregnancy. We measured non-fasting lipids, glucose and insulin blood concentrations of their children at a mean age of 9.7 (standard deviation 0.2) years. Analyses were performed for boys and girls separately. ResultsAn interquartile range (IQR) higher natural log transformed third trimester maternal urine phthalic acid concentration was associated with a 0.20 (95% confidence interval (CI) 0.07–0.34) standard deviation score (SDS) higher triglycerides concentration among boys. Maternal bisphenol urine concentrations were not associated with non-fasting lipid concentrations during childhood. An IQR higher natural log transformed second trimester maternal high molecular weight phthalates (HMWP) and di-2-ethylhexylphthalate (DEHP) urine concentration were associated with a 0.19 (95% CI 0.31–0.07) respectively 0.18 (95% CI 0.31–0.06) SDS lower glucose concentration among boys. An IQR higher natural log transformed third trimester maternal bisphenol F urine concentration was associated with a 0.22 (95% CI 0.35–0.09) SDS lower non-fasting insulin concentration among boys. ConclusionsOur results suggest potential persisting sex specific effects of fetal exposure to phthalates and bisphenols on childhood lipid concentrations and glucose metabolism. Future studies are needed for replication and exploring underlying mechanisms.

Maternal Bisphenol S exposure affects the reproductive capacity of F1 and F2 offspring in mice

Bisphenol S (BPS) is an endocrine disruptor which is widely used in commercial plastic products. Previous studies have shown that exposure to BPS has toxic effects on various aspects of mammalian, but there are few reports about reproductive toxicity. In order to investigate the effects of maternal BPS exposure on the reproductive of F1 and F2 female mice, the pregnant mice were orally administered with different dosages of BPS only once every day from 12.5 to 15.5 days post-coitus (dpc). The results showed that maternal BPS exposure to 2 μg per kg of body weight per day (2 μg/kg) and 10 μg/kg accelerated the meiotic prophase I (MPI) of F1 female mice and the expression of the genes related to meiotic were increased. Further studies showed that maternal BPS exposure resulted in a significant increase in the percentage of oocytes enclosed in primordial follicles in the 3 days post-partum (3 dpp) ovaries of F1 female mice. And at the time of 21 days post-partum (21 dpp) in F1 female mice, the number of antral follicles were significantly lower compare to controls. In the study of five-week female mice of F1, we found that BPS disturbed the folliculogenesis, and the maturation rates and fertilization rates of oocytes were significantly decreased. Of note, maternal BPS exposure disrupted H3K4 and H3K9 tri-methylation levels in F1 ovaries. Maternal BPS exposure only affected the cyst breakdown in F2 female mice. Taken together, our results suggest that, maternal BPS exposure impaired the process of meiosis and oogenesis of F1 and F2 offspring, resulting in abnormal follicular development and serious damage to the reproduction.

A birth cohort study of the association between prenatal serum bisphenol A concentration and infant neurobehavior development

Objective: To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant. Methods: Participants were from the Ma'anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants' neurobehavioral development. Results: A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants' neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M (P25,P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant's development of social behavior [β (95%CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with β (95%CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion: BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.

Metabolic Effects of Maternal Bisphenol F Exposure in Population‐based Heterogeneous Stock Rats

Bisphenol F (BPF) is marketed as a ‘safe’ substitute for bisphenol A (BPA), a risk factor for obesity and heart disease, in manufacturing polycarbonates and in common consumer products. BPF’s environmental presence is growing rapidly and is detected in 66.5% of U.S. adults. There is evidence of individual variation in bisphenol levels, suggesting that gene x environment (GxE) interactions influence risk of cardiometabolic disease from bisphenol exposure. Few studies of BPF exposure in either humans or animals have been performed, thus their associated health risks are mostly unknown. Traditional in vivo toxicity studies are performed in genetically undefined outbred rats or genetically homogeneous inbred mice, leading to conflicting results possibly due to GxE interactions. The N/NIH Heterogeneous Stock (HS) rats are outbred rats that better model humans yet are amenable to genetic study. Our overall hypothesis is that BPF exposure is a cardiometabolic disease risk factor based on underlying genetic susceptibility, which can be identified using the HS rat model.We previously demonstrated that five weeks of post‐wean BPF exposure significantly impacts body growth and adiposity in male HS rats. The goal of this project was to determine if maternal BPF exposure also influences growth and adiposity in HS rats, since maternal exposure to BPA is known to impact the metabolic health of both the mother and offspring. HS female breeders were randomly selected for exposure to either vehicle (0.1% Ethanol), 0.1125 mg/L BPF in 0.1% Ethanol (Low Dose), or 1.125 mg/L BPF in 0.1% Ethanol (High Dose) in drinking water during gestation and lactation (~6 weeks total exposure time). One pup of each sex was weaned at 3 weeks of age with no additional exposure. Tissues were taken from dams. Weight and adiposity measures were obtained from weanlings until 8 weeks of age.Our study determined that dams exposed to High Dose showed significantly increased gonadal white adipose tissue (GWAT) mass and trended increased brown adipose tissue (BAT) mass (Table 1). Maternal High Dose exposure impacted weanling body composition at 7 weeks of age as measured by nuclear magnetic resonance (NMR), with the female weanlings significantly increasing %fat mass and trending decreased %lean mass. Maternal BPF exposure also impacted weanling BAT mass, with High Dose female weanlings trending increased BAT mass. No differences were found in male offspring. Our preliminary data suggest that maternal BPF exposure alters adiposity of both the HS dams and female offspring. This work supports BPF exposure as a cardiometabolic disease risk factor and indicates that the HS rat will be a useful model for dissecting GxBPF interactions on metabolic health.Support or Funding InformationNIH P30 ES005605, National Institutes of Health Predoctoral Training Grant T32GM008629 Subject Phenotype Vehicle Low Dose High Dose Dam % BAT (mg) 313 ± 14 343 ± 20 370 ± 31 GWAT (g) 5.7 ± 0.4 5.3 ± 0.5 7.9 ± 0.8 * Female Weanling # Fat % 9.9 ± 1.1 14.0 ± 2.9 17.0 ± 2.0 * Lean % 73.0 ± 1.1 69.3 ± 2.6 66.4 ± 1.7 BAT (mg) 175 ± 9 180 ± 10 213.8 ± 23 Values: mean ± SEM %Vehicle n = 10, Low Dose n = 9, High Dose n = 5 #Vehicle n = 10, Low Dose n = 10, High Dose n = 8 (NMR Vehicle n = 8, Low Dose n = 6, High Dose n = 4) *p &lt; 0.05 High Dose vs Vehicle (linear mixed model regression, Likelihood Ratio Test)