In vivo effects of low dose prenatal bisphenol A exposure on adiposity in male and female ICR offspring

Abstract

Background: Bisphenol A (BPA) is known to exhibit endocrine disrupting activities and is associated with adiposity. We examined the obesogenic effect of prenatal BPA exposure in the present study. Methods: Pregnant ICR mice were exposed to vehicle or BPA via the drinking water at a dose of 0.5 μg/kg·d throughout the gestation. Obesity-related indexes were investigated in the 12-wk-old offspring. Primary mouse embryonic fibroblasts (MEFs) collected from treated embryos were used to test effects of BPA on adipocyte differentiation. Results: Offspring presented a significantly higher rate of weight gain than the control, with impaired insulin sensitivity and increased adipocyte size. Differentiation of MEFs from BPA-treated mice showed a higher propensity for the adipocyte commitment as well as up-regulation of genes enriched in lipid biosynthesis. TGF-β signaling pathway was found to modulate obesogenic effect of BPA in MEF model, but estrogen signaling pathway had no effect. Conclusions: The present study provides strong evidence of the association between prenatal exposure to low dose of BPA and a significant increase in body weight in the offspring mice with a critical role played by TGF-β signaling pathway. The potential interactions modulating the binding of BPA and TGF-β that activate its obesogenic effects need to be examined.

Keywords

• Bisphenol A
• Prenatal exposure
• Offspring obesity
• TGFβ