Maternal Bisphenol A Exposure Research Articles

Associations between prenatal exposure to bisphenol a and neonatal outcomes in a Taiwanese cohort study: Mediated through oxidative stress?

This study determined whether maternal bisphenol A (BPA) exposure influences birth outcomes through oxidative stress and estimated the daily intake of BPA through breast milk for infants. One hundred and eighty-six pregnant women without pregnancy complications were enrolled and maternal urine was collected in the third trimester. Postnatal breast milk was collected in the first and third months after delivery. Concentrations of BPA were determined through ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the effects of BPA exposure and oxidative stress levels on birth outcomes. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to maternal BPA exposure on birth outcomes. The daily intake of BPA in breast milk was calculated using probabilistic risk assessment methods. The geometric means (geometric standard deviation) of BPA levels for maternal urine and first- and third-month breast milk were 2.19 (2.88) μg/g creatinine., 1.35 (3.53) ng/g, and 3.17 (2.97) ng/g, respectively. No significant mediation existed among maternal BPA exposure, oxidative stress level, and neonatal head circumference. Three percent of 1-monthold babies and 1% of 3-month-old babies exceeded the BPA tolerable daily intake of 4 μg/kg-bw/day proposed by the European Food Safety Authority. This study revealed the BPA exposure profile for pregnant women and infants in northern Taiwan. The marginally significant correlation between maternal BPA exposure and neonatal head circumference should be considered.

Sex Differences in the Effects of Prenatal Bisphenol A Exposure on Genes Associated with Autism Spectrum Disorder in the Hippocampus

Autism spectrum disorder (ASD) is a neurodevelopmental disorder inexplicably biased towards males. Although prenatal exposure to bisphenol A (BPA) has recently been associated with the ASD risk, whether BPA dysregulates ASD-related genes in the developing brain remains unclear. In this study, transcriptome profiling by RNA-seq analysis of hippocampi isolated from neonatal pups prenatally exposed to BPA was conducted and revealed a list of differentially expressed genes (DEGs) associated with ASD. Among the DEGs, several ASD candidate genes, including Auts2 and Foxp2, were dysregulated and showed sex differences in response to BPA exposure. The interactome and pathway analyses of DEGs using Ingenuity Pathway Analysis software revealed significant associations between the DEGs in males and neurological functions/disorders associated with ASD. Moreover, the reanalysis of transcriptome profiling data from previously published BPA studies consistently showed that BPA-responsive genes were significantly associated with ASD-related genes. The findings from this study indicate that prenatal BPA exposure alters the expression of ASD-linked genes in the hippocampus and suggest that maternal BPA exposure may increase ASD susceptibility by dysregulating genes associated with neurological functions known to be negatively impacted in ASD, which deserves further investigations.

Transgenerational effects of maternal bisphenol A exposure on offspring metabolic health - Erratum.

Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.

Prenatal bisphenol A exposure is associated with language development but not with ADHD-related behavior in toddlers from the Odense Child Cohort

Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities widely used in a variety of consumer products. The fetal brain is particularly sensitive to chemical exposures due to its rapid growth and complexity. Some studies have reported associationbetween maternal BPA exposure and behavior but few have assessed impact on cognitive development, and to our knowledge no studies have specifically assessed the impact on language development. We therefore assessed whether maternal urinary BPA concentration during pregnancy was associated with language development and attention-deficit and hyperactivity disorder (ADHD) symptoms in offspring aged 18–36 months in the prospective Odense Child Cohort. BPA was analyzed in 3rd trimester maternal fasting urine spot samples. Language development was addressed among 535 children using the Danish adaptation of the MacArthur-Bates Communicative Development Inventories at median age 21 months; ADHD traits were assessed by parents of 658 children using the Child Behavior Checklist for ages 1½-5 years at mean age 2.7 years. Associations were assessed using logistic regression models comparing children below the 15th percentile score for language and above the 85 percentiles score for ADHD with the other children while stratifying by sex and adjusting for maternal education, duration of breastfeeding and maternal urine phthalates. BPA was detected in 85.3% of the urine samples (median 1.2 ng/ml). Boys of mothers with BPA exposure in the highest tertile had an odds ratio of 3.70 (95% CI 1.34–10.21) of being in the lowest 15th percentile of vocabulary score compared to boys of mothers within the lowest tertile of BPA exposure after adjustment, whereas no association was found in girls. No clear dose-response relationship between maternal BPA and ADHD scores above the 85th percentile was found for either sex. Since early language development is a predictor of future reading skills and educational success, more epidemiological studies assessing BPA exposure and language skills are needed to confirm our findings.

Transgenerational effects of maternal bisphenol: a exposure on offspring metabolic health.

Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.

Prenatal Bisphenol A Exposure and Brain Structure in Preschool-Aged Children

Background/Aim: In Canada, over 90% of the population has detectable levels of bisphenol A (BPA) due to dietary and non-dietary exposure. Human epidemiological studies have demonstrated behavioral effects of BPA exposure in children. Further, reported effects have been found to be sex-specific. Although behavioral outcomes have been examined, there is limited understanding of the effects of BPA exposure on children’s brain structure. This study examined the effects of maternal BPA exposure on subsequent child white matter brain structure at 3 to 6 years of age.Method: Maternal total BPA concentrations in spot urine samples obtained during the second trimester of pregnancy were analyzed for 99 women. Their children participated in magnetic resonance imaging (MRI) between 3 to 6 years of age. Associations between prenatal BPA exposure and child fractional anisotropy and mean diffusivity within 10 isolated white matter tracts were investigated, controlling for sex and total maternal creatinine levels. Anisotropy and diffusivity provide measures of white matter structure and maturity.Results: Significant positive associations were observed between the level of prenatal BPA exposure and child white matter mean diffusivity within the splenium, and the right inferior frontal occipital, inferior longitudinal fasciculus, uncinated fasciculi, and pyramidal fibers. Significant sex differences were found, with more associations noted among females. No associations were observed between prenatal BPA exposure and child white matter anisotropy.Conclusions: Higher prenatal BPA exposure was related to higher mean diffusivity in white matter tracts at 3 to 6 years of age. Developmental studies show that with age, white matter anisotropy increases and diffusivity decreases in typically developing children. The current findings suggest that exposure to higher levels of BPA prenatally may be related to reduced white matter maturity in preschool aged children.

Maternal Bisphenol A exposure impaired endochondral ossification in craniofacial cartilage of rare minnow (Gobiocypris rarus) offspring

Bisphenol A (BPA), an endocrine disrupting compound, is present in the aquatic environment. BPA can mimic estrogen and cause adverse effects on development and reproduction in different organisms. As epigenetic modifications due to BPA exposure have been reported, the interest on the effects of this chemical has increased. To assess the potential effects of maternal BPA exposure on offspring bone development, adult Gobiocypris rarus (G. rarus) females were exposed to 15 μg L−1 and 225 μg L−1 BPA for 21 days. Eggs were collected after artificial spawning and fertilized with the fresh milt of non-exposed male fish. The offspring were raised in clean water and randomly selected for examination at different development stages. Our results showed that specific effects including poor quality of the embryos, increased malformation (bent spine and tail), and delayed craniofacial cartilage ossification of the larvae. Additionally, the transcripts of ossification related genes were significantly downregulated in offspring, and the lysyloxidase activity decreased. The present study demonstrated the maternal-mediated skeleton toxicity of BPA and its adverse effects on G. rarus.

Exposure to bisphenol A during maternal pregnancy and the emotional and behavioral impact on their preschool children

Objective: To explore the long-term effects of maternal pregnancy bisphenol A (BPA) exposure on emotional and behavioral problems appeared in their preschool children. Methods: The study sample was a subset of the China-Anhui Birth Cohort Study (C-ABCS). A unified questionnaire was used to collect basic information on both pregnant women and their children. Free BPA concentration in maternal serum was determined by high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS). The parent-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to estimate the emotional and behavioral problems in preschool children. A total of 1 713 pairs of mothers and children were included in this study. Association between BPA exposure during pregnancy and the emotional and behavioral problems in preschool children was evaluated with multinomial logistic regression model. Results: Prevalence rates in 1 713 preschool children appeared as: 6.48% of emotional problems, 8.11% for conduct problems, 8.35% for hyperactivity/inattention, 2.86% for peer problems, 11.38% for prosocial behaviors and 7.94% for total difficulties. Subjects were divided according to the degrees of exposure and the results showed as: low exposure group (≤0.120 ng/ml), medium exposure group (0.120<BPA<0.400 ng/ml) and high exposure group (≥0.400 ng/ml) according to the serum BPA concentration in tertile. Results from the multivariate logistic regression analysis showed that high level of maternal BPA exposure appeared a risk factor on children's abnormal conducts (OR=1.876, 95% CI: 1.161-3.029), more obvious in boys (OR=2.291, 95%CI: 1.126-4.661). Conclusion: Maternal exposure to high level of BPA during pregnancy might increase the detrimental effects of abnormal conducts in their preschool children, more obviously seen in boys.

Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study.

BackgroundAlthough recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. MethodsWe conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. ResultsBPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). ConclusionsThese results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia.

Effects of maternal or paternal bisphenol A exposure on offspring behavior

Bisphenol A (BPA) is an endocrine disrupting chemical used in the production of polycarbonate plastics and resins. Exposure to BPA during gestation has been proposed as a risk factor for the development of neurobehavioral disorders, such as autism spectrum disorder. To address the behavioral impact of developmental exposure to BPA, we tested offspring of mice exposed to a daily low dose of BPA during pregnancy. We also asked if preconception exposure of the sire affected behaviors in offspring. Sires that consumed BPA for 50days prior to mating weighed less than controls, but no effects on any reproductive measures were noted. Juvenile offspring exposed to BPA maternally, but not paternally, spent less time in the open arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. However, neither parental exposure group differed significantly from controls in the social recognition task. We also assessed the behaviors of maternally exposed offspring in two novel tasks: ultrasonic vocalizations (USVs) in pups and operant reversal learning in adults. Maternal BPA exposure increased the duration and median frequency of USVs emitted by pups during maternal separation. In the reversal learning task, females responded more accurately and earned more rewards than males. Additionally, control females received more rewards than BPA females during the acquisition phase of the task. These are among the first studies conducted to ask if BPA exposure via the sire affects offspring behavior and the first study to report effects of gestational BPA exposure on pup USVs and adult operant responding.

Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring.

Background:Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring.Objective:We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets.Methods:Cellular and molecular mechanisms underlying these persistent changes were determined in F1 and F2 adult offspring of F0 mothers exposed to two relevant human exposure levels of BPA ( and ).Results:Both doses of BPA significantly impaired insulin secretion in male but not female F1 and F2 offspring. Surprisingly, LowerB and UpperB induced islet inflammation in male F1 offspring that persisted into the next generation. We also observed dose-specific effects of BPA on islets in males. UpperB exposure impaired mitochondrial function, whereas LowerB exposure significantly reduced mass and increased death that persisted in the F2 generation. Transcriptome analyses supported these physiologic findings and there were significant dose-specific changes in the expression of genes regulating inflammation and mitochondrial function. Previously we observed increased expression of the critically important gene, Igf2 in whole F1 embryos. Surprisingly, increased Igf2 expression persisted in the islets of male F1 and F2 offspring and was associated with altered DNA methylation.Conclusion:These findings demonstrate that maternal BPA exposure has dose- and sex-specific effects on pancreatic islets of adult F1 and F2 mice offspring. The transmission of these changes across multiple generations may involve either mitochondrial dysfunction and/or epigenetic modifications. https://doi.org/10.1289/EHP1674

Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs.

This study was conducted to explore whether exposure to bisphenol A (BPA) during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET) could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON); control diet supplemented with BPA (50 mg/kg); control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 μg/kg vitamin B12, and 15 mg/kg folic acid); and control diet with BPA and MET supplementation (BPA + MET). Intestine samples were collected from pigs’ offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1) and DNA methyl transferase 3a (DNMT3a), and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT), DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR), and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05). Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring’s intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation.

Les relations entre le bisphénol A et les troubles du spectre autistique se précisent : la sérotonine est-elle le lien manquant ?

The etiology of autism spectrum disorders (ASD) is believed to be multifactorial and to involve genetic and environmental components. Environmental chemical exposures are increasingly understood to be important in causing neurotoxicity in fetuses and newborns. Recent data from the Centers for Disease Control and Prevention in the United States suggest a substantial increase in ASD prevalence, only partly explicable by factors such as diagnostic substitution. Bisphenol A (BPA) is an ubiquitous xenoestrogen widely employed in a variety of consumer products including plastic and metal food and beverage containers, dental sealants and fillings, medical equipment and thermal receipts. Therefore, most people are exposed almost continuously to BPA in industrialized countries. Sources of BPA exposure are predominantly diet, but also through inhalation or dermal absorption. BPA can be measured in many human fluids and tissues including saliva, serum, urine, amniotic fluid, follicular fluid, placental tissue and breast milk. There is concern that BPA exposure may influence human brain development and may contribute to the increasing prevalence of neurodevelopmental and behavioural problems. Epigenetic mechanisms are suggested by a mouse study that demonstrated that BPA exposure during gestation had long lasting, transgenerational effects on social recognition. Previous epidemiological studies suggested a relationship between maternal BPA exposure and ASD. A recent study of 46 children with ASD and 52 controls found for the first time a direct association between children with ASD and BPA exposure and demonstrated that BPA is not metabolized well in children with ASD. The metabolomic analyses showed a correlation between ASD and essential amino acid metabolism pathways. Essential amino acids are precursors of neurotransmitters, for example tryptophan for serotonin. Fetal and prenatal BPA exposure was suggested to perturb the serotonergic system in rat and mice models. On the other hand, hyperserotonemia was reported in approximately one-third of autistic patients and also in relatives. Moreover, neuroimaging studies revealed two fundamentally different types of serotonin synthesis abnormality in children with autism compared to age-matched nonautistic children, a difference in whole-brain capacity and focal abnormalities. Finally, decreased serotonin transporter and serotonin receptor binding have been reported in both children and adults with autism. So, the link between BPA and autism could be a defect of the normal in utero or perinatal serotonergic system development. In France, BPA was banned in baby bottles in 2010 and in any food or beverage packaging since January 2015. Therefore, there is an urgent need to find safe alternatives in the use of BPA in the manufacture of industrial products.

Erratum to: Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women.

Introduction Estrogen inhibits lactation and bisphenol A (BPA) is a high production environmental estrogen. We hypothesize an inhibitory effect of BPA on lactation and aim to analyze the association between third trimester pregnancy urinary BPA and breastfeeding rates 1 month postpartum. Methods Odds ratios (OR) and 95 % confidence intervals (95 % CI) of breastfeeding and perceived insufficient milk supply (PIM) in relation to maternal peripartum urinary BPA concentrations were calculated in 216 mothers. Results 97.2 % of mothers in the lowest BPA tertile were breastfeeding at 1 month postpartum, compared to 89.9 % in highest (p = 0.01). Adjusted ORs (95 % CI) for not breastfeeding at 1 month were 1.9 (0.3, 10.7) and 4.3 (0.8, 21.6) for second and third BPA tertiles, respectively, compared to the lowest (p = 0.06, trend). 4.2 % reported PIM in the lowest BPA tertile, compared to 8.7 % in the highest (p = 0.03). Adjusted ORs (95 % CI) for PIM were 1.8 (0.4, 7.7) and 2.2 (0.5, 9.5), for the second and third BPA tertiles, respectively, compared to the lowest (p = 0.29, trend). Discussion These results suggest an association between maternal BPA exposure and decreased breastfeeding.

Association of Bisphenol A Exposure with Breastfeeding and Perceived Insufficient Milk Supply in Mexican Women.

Introduction Estrogen inhibits lactation and bisphenol A (BPA) is a high production environmental estrogen. We hypothesize an inhibitory effect of BPA on lactation and aim to analyze the association between third trimester pregnancy urinary BPA and breastfeeding rates 1month postpartum. Methods Odds ratios (OR) and 95% confidence intervals (95% CI) of breastfeeding and perceived insufficient milk supply (PIM) in relation to maternal peripartum urinary BPA concentrations were calculated in 216 mothers. Results 97.2% of mothers in the lowest BPA tertile were breastfeeding at 1month postpartum, compared to 89.9% in highest (p=0.01). Adjusted ORs (95% CI) for not breastfeeding at 1month were 1.9 (0.3, 10.7) and 4.3 (0.8, 21.6) for second and third BPA tertiles, respectively, compared to the lowest (p=0.06, trend). 4.2% reported PIM in the lowest BPA tertile, compared to 8.7% in the highest (p=0.03). Adjusted ORs (95% CI) for PIM were 1.8 (0.4, 7.7) and 2.2 (0.5, 9.5), for the second and third BPA tertiles, respectively, compared to the lowest (p=0.29, trend). Discussion These results suggest an association between maternal BPA exposure and decreased breastfeeding.

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

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

Epigenetic disruption and glucose homeostasis changes following low-dose maternal bisphenol A exposure.

Developmental exposure to bisphenol A (BPA) has been linked to impaired glucose homeostasis and pancreatic function in adulthood, which has been hypothesized to result from the disruption of pancreatic β-cell development at early life. Here we evaluated whether maternal BPA exposure disrupts β-cell development and glucose tolerance and the role of epigenetic modifications of key regulator in this process. We found that maternal exposure to BPA (10 μg kg-1 d-1) reduced the pancreatic β-cell mass and the expression of pancreatic and duodenal homeobox 1 (Pdx1) at birth, as well as the expression of Pdx1 at gestational day (GD) 15.5. In parallel with the decreased expression of Pdx1, histones H3 and H4 deacetylation, along with demethylation of histone 3 lysine 4 (H3K4) and methylation of histone 3 lysine 9 (H3K9), were found at the promoter of Pdx1, while no significant changes in DNA methylation status were detected at this region. Moreover, these alterations were observed in adult life along with impaired glucose tolerance. We conclude that maternal exposure to BPA reduces pancreatic β-cell mass at birth by reducing PDX1+ progenitors during fetal development through altering the histone modifications of Pdx1, which can be propagated to later life and increase the susceptibility to glucose intolerance.

Pregnancy is a new window of susceptibility for bisphenol a exposure.

Pregnancy is a new window of susceptibility for bisphenol a exposure.

Interaction between GSTM1/GSTT1 Polymorphism and Prenatal Bisphenol A Exposure on Infant Neurodevelopment at 6 Months

Interaction between GSTM1/GSTT1 Polymorphism and Prenatal Bisphenol A Exposure on Infant Neurodevelopment at 6 MonthsAbstract Number:2279 Eun-Kyo Park*, HyeSook Park, Yun-Chul Hong, Mina Ha, Yangho Kim, Byung-Mi Kim, Eunjeong Kim, and Eun-Hee Ha Eun-Kyo Park* Department of Preventive Medicine, School of Medicine, Ewha Womans University, Korea, E-mail Address: [email protected] Search for more papers by this author , HyeSook Park Department of Preventive Medicine, School of Medicine, Ewha Womans University, Korea, E-mail Address: [email protected] Search for more papers by this author , Yun-Chul Hong Department of Preventive Medicine, College of Medicine, Seoul National University, Korea, E-mail Address: [email protected] Search for more papers by this author , Mina Ha Department of Preventive Medicine, College of Medicine, Dankook University, Korea, E-mail Address: [email protected] Search for more papers by this author , Yangho Kim Department of Occupational and Environmental Medicine, Ulsan University Hospital, Korea, E-mail Address: [email protected] Search for more papers by this author , Byung-Mi Kim Department of Preventive Medicine, School of Medicine, Ewha Womans University, Korea, E-mail Address: [email protected] Search for more papers by this author , Eunjeong Kim Department of Preventive Medicine, School of Medicine, Ewha Womans University, Korea, E-mail Address: [email protected] Search for more papers by this author , and Eun-Hee Ha Department of Preventive Medicine, School of Medicine, Ewha Womans University, Korea, E-mail Address: [email protected] Search for more papers by this author AbstractBACKGROUND : The few studies have suggested that prenatal Bisphenol A (BPA) exposure may be linked to infantile neurodevelopment. Glutathione S-transferases (GSTs) provide antioxidant defense against oxidative stress in all the vital tissues. We investigated the interaction between GSTM1/GSTT1 Polymorphism and prenatal BPA exposure on infant neurodevelopment at 6 months.METHODS : The prospective cohort study of Mothers and Children's Environmental Health (MOCEH) was built up in 2006 and the study subjects were restricted to those for whom BPA and GSTM were assessed and 575 mother–infant pairs were eligible. The total urinary concentration of BPA was measured from mothers during their late pregnancy. The Mental (MDI) and Psychomotor (PDI) Development Index scores of the infants were assessed by using the Bayley Scales of Infant Development. The genotyping of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms were carried out by using polymerase chain reaction. We performed a multiple linear regression model for statistical analyses (SAS 9.3).RESULTS : The BPA concentration was 1.14 ug/g creatinine in maternal urine. MDI at 6 months was inversely associated with the natural log concentrations of maternal BPA (ß=-0.0107, p=0.005). Infant neurodevelopment at 6 months decreased with increasing maternal BPA whose mothers had the either GSTT1/GSTM1 null type (ß=-0.0111, p=0.010). However, there was no significantly inverse relationship between BPA and infant neurodevelopment at 6 months in the GSTM1 and GSTT1 present genotypes.CONCLUSION : We found the association between maternal BPA exposure and infant neurodevelopment was differed by GSTT1/GSTM1 null type. ACKNOWLEDGMENT : This study was supported by MOCEH (Mothers and Children’s Environmental Health) project of the National Institute of Environmental Research, Republic of Korea.

Maternal Urinary Bisphenol a during Pregnancy and Maternal and Neonatal Thyroid Hormone Concentrations

Bisphenol A (BPA) is an endocrine disruptor present in many consumer products. Experimental and epidemiologic evidence suggest that BPA disrupts thyroid function. The only prior epidemiologic study of prenatal BPA exposure reported sex-specific effects on thyroid hormones (THs). We examined associations between BPA and THs using multivariable linear regression in the Health Outcomes and Measures of the Environment Study (2003- 2006, Cincinnati, Ohio), a prospective birth cohort. Maternal urinary BPA concentration was measured at approximately 16 and 26 weeks gestation. Free and total thyroxine (T4) and thyroid stimulating hormone (TSH) concentrations were measured in maternal serum at approximately 16 weeks (n=185) and in cord serum (n=252). Separate models were built for a) 16 weeks, b) 26 weeks, and c) 16 and 26 weeks average urinary BPA. We found no associations between 16-week BPA concentration and maternal THs, and between any of the BPA measurements and cord T4. In contrast, each 10-fold increase in average maternal urinary BPA was associated with decreased cord TSH in female newborns (percent change=-31%; 95% confidence interval (CI):-49, -8%) but not males (3%; 95% CI:-26, 42%; p for effect modification=0.04). The 16-week BPA concentration was not associated with TSH (females:-7%; 95% CI:-32, 28%; males:-2%; 95% CI:-33, 42%; p for effect modification=0.87). In contrast, 26-week maternal urinary BPA was associated with reduced TSH for females (-43%; 95% CI:-60, -18%) but not males (-1%; 95% CI:-20, 24%; p for effect modification=0.01). We did not observe associations between BPA and maternal THs during pregnancy or newborn T4. In contrast with one prior study reporting reduced TSH among male newborns only, our findings suggest that prenatal BPA exposure may reduce TSH among female newborns. Consistent with the prior study, maternal BPA exposure later in pregnancy may have greater influence on newborn TSH than in early pregnancy.