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

Abstract

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 μM 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 (Δ Ψ 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 Δ Ψ m, the release of cytochrome c into the cytosol and further the activation of caspase cascade.