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

• BPA was examined for its effects on cultured rat Sertoli cells.
• Apoptosis-caused cell death was observed in cells exposed to 50 and 70 μM BPA.
• Fas/FasL plays a critical role in BPA-induced cells apoptosis.
• JNKs/p38 MAPK and NF-κB were activated after cells exposure to BPA.

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 μM) 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 μM 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-κB into nuclei indicated the activation of NF-κB 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-κB, and Fas/FasL system plays a critical role in the initiation of apoptosis.