BPA-induced apoptosis of rat Sertoli cells through Fas/FasL and JNKs/p38 MAPK pathways

Bisphenol-A was examined for its effects on cultured Sertoli cells established from 18 to 22-day-old rat testes. Results indicated that exposure to BPA (0, 30, 50 and 70 mu M) decreased the cell viability in a concentration-dependent manner and induced cell apoptosis. Apoptosis-caused cell death was observed in cells exposed to 50 and 70 mu M BPA. The mRNA expressions of Fas, FasL and caspase-3 were all elevated, and the protein expressions of FasL and cleaved caspase-3 were also increased. In addition, levels of phosphorylation of JNKs/p38 MAPK were also increased and then activated JNKs/p38 MAPK up regulated target gene expressions, such as c-jun and CHOP. Translocation of NF-kappa B into nuclei indicated the activation of NF-kappa B after treatment with BPA. Taken together, observed results suggest that BPA induces apoptosis of Sertoli cells by the activation of JNKs/p38 MPAK and translocation of NF-kappa B, and Fas/FasL system plays a critical role in the initiation of apoptosis. (C) 2014 Elsevier Inc. All rights reserved.