Developmental toxicity of bisphenol-A on post-implantation rat embryos cultured in vitro

Abstract

We studied the developmental toxicity and possible mechanisms of bisphenol A (BPA) damage of rat embryos in vitro. Whole-embryo culture was used to study the damage of BPA on visceral yolk sacs (VYSs) and embryos. Micromass culture was used to investigate the effects of BPA on differentiation and proliferation of embryonic midbrain cells. Neutral red staining was used to detect cell death. Immunohistochemistry was used to evaluate the expression of inducible nitric oxide synthase (iNOS) in VYSs and embryos. Our results as following, BPA could cause damage to embryonic development and morphological differentiation in a dose-dependent manner. At the highest dose, 80 and 100 mg/l BPA delayed cardiac tube growth and differentiation of VYSs, and induced various embryonic defects. BPA also induced excessive cell death and inhibited both proliferation and differentiation of rat midbrain cells. Immunohistochemical staining showed that BPA induces abnormal expression of iNOS protein in treated VYSs and embryos. Our results indicated that BPA is a potential teratogen and has toxicity on cultured rat embryo development. BPA-related developmental toxicity is caused by damage to the VYS, excessive cell death, inhibition of cell proliferation and differentiation, and abnormal expression of iNOS. ©2010 The Pharmaceutical Society of Japan.