Bisphenol A Exposure, Adipogenic Mechanism and Effect on Childhood Adiposity

Bisphenol A (BPA) is a common component in plastic consumer products and epoxy resin linings. Initially developed in the 1930s-40s as a synthetic hormone treatment, it is now widely considered an endocrine disrupting chemical (EDC). To answer the question of both timing and developmental origin of BPA effects on adipogensis, we employed both an epidemiological approach, and experimental methodologies using primordial cell lines, mesenchymal stem cells (MSCs). Our study characterizes early life exposures to BPA, explores the adipogenic mechanism of BPA in human MSCs via cellular morphometrics and PPARgamma gene expression, and identifies associations between early life exposure to BPA and childhood obesity and adiposity.;For our epidemiological assessments, we studied a birth cohort of African American and Dominican mother and child dyads in New York City. BPA was detected in nearly all urine samples from prenatal third trimester and childhood ages 3 years, 5 years and 7 years. Prenatal urinary BPA concentrations were significantly lower than postnatal urinary BPA concentrations (p<0.001). BPA and phthalate metabolites were correlated prenatally and at 3, 5, and 7 years (all p-values ≤ 0.02). BPA concentrations were correlated with phthalate metabolite concentrations prenatally, and at 3, 5 and 7 years(all p-values < 0.05). Geometric means of BPA were higher among African Americans than among Dominicans in prenatal (p<0.01), 5 year (p<0.001) and 7 year (p=0.02) samples. Postnatal BPA concentrations were significantly higher among children with mothers who had never married marital status and were significantly higher in summer than in all other seasons (all p-values < 0.05). These findings reveal widespread BPA exposure in an inner-city minority population.;Our in vitro experiment was a feasibility study which sought to determine whether exposure to BPA by human umbilical cord mesenchymal stem cells (HUMSC) induces morphological changes and PPARgamma gene expression during adipogenesis. A significant decrease in surface area was seen in cells exposed to 100 muM concentration of BPA as compared to exposure to standard induction medium at day 14 (t=-37.02 p=0.001). Differences in cell surface area were not observed at day 21. A twofold increased expression of PPARgamma1 was observed in cells exposed to 10 muM concentration of BPA by 72 hours of adipogenic induction which was higher than the increase in expression observed for cells exposed to the positive control induction medium containing 10 muM concentration of rosiglitazone. All induction media conditions had negligible effects on PPARgamma2 expression. As BPA increases expression of PPARgamma1 in HUMSCs during the transition into the early terminal differentiation phase of adipogenesis, HUMSCs may be an approximate target tissue for evaluating BPA effects in adipogenesis.;Finally, using a longitudinal research design, we analyzed the possible effect of prenatal and postnatal BPA exposures, measured in urine, on childhood anthropometric outcome measures. Participants in the CCCEH have been followed since the third trimester of pregnancy, providing us with anthropometric data on children from birth through the age of seven years. Available anthropometric outcome measures include body mass index z-scores (BMIZ) at 5 and 7 years, as well as fat mass index (FMI), percent body fat (%BF), and waist circumference (WC) at 7 years. Prenatal urinary BPA concentrations were positively associated with child age 7 FMI (beta=0.31 kg/m2, p-value=0.04, [95%CI 0.01, 0.60]), %BF (beta=0.79, p-value=0.04, [95%CI 0.03, 1.55]), and WC (beta=1.29 cm, p-value=0.01, [95%CI 0.29, 2.30]). Child urinary BPA concentrations were not associated with childhood BMI or other anthropometric outcomes. As the prenatal exposures were associated with childhood measures of adiposity, prenatal BPA exposure may have an effect on adiposity as children age that cannot be determined by the use of BMI alone. Our results suggest BPA may contribute to the developmental origins of obesity and adiposity. (Abstract shortened by UMI.).