p,p′-DDE induces mitochondria-mediated apoptosis of cultured rat Sertoli cells

p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenoxytrichloroethane (DDT), is a known persistent organic Pollutant and male reproductive toxicant. However, the mechanism underlying male reproductive toxicity of p.p'-DDE remains limited. In the present study, Sertoli cells were used to investigate the molecular mechanism involved in p,p'-DDE's male reproductive toxicity. Results showed that p,p'-DDE exposure at over 30 mu M showed induction of apoptotic cell death. p.p'-DDE could induce mitochondria-mediated apoptotic changes including elevation in reactive oxygen species (ROS) generation, decrease in mitochondrial membrane potential (Delta Psi(m)), and release of cytochrome c into the cytosol, which Could be blocked by antioxidant agent N-acetyl-L-cysteine (NAC). In addition, elevated ratios of Bax/Bcl-w and Bak/Bcl-w and cleavages of procaspase-3 and -9 were induced by p,p'-DDE treatment. All of the results suggested that ROS generation may play a critical role in the initiation of p,p'-DDE-induced apoptosis by mediation of the disruption of the release of cytochrome c into the cytosol and further the activation of caspase cascade. (c) 2008 Elsevier Ireland Ltd. All rights reserved.