p,p'-DDE induces apoptosis and mRNA expression of apoptosis-associated genes in testes of pubertal rats.

One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. To elucidate the mechanism underpinning the testicular effects of p,p'-DDE, we sought to investigate apoptotic effects and mRNA expression of apoptosis-associated genes in the testis of pubertal rats, including Fas, FasL, calpain-1, cytochrome c, Bax, Bcl-w, Bak, and caspase-3, -8, -9, -12. Animals were administered with different doses of p,p'-DDE (0, 20, 60, 100 mg/kg body weight) every other day by intraperitoneal injection for 10 days. The results indicated that p,p'-DDE exposure at over 20 mg/kg body weight showed the induction of apoptotic cell death. p,p'-DDE could induce decrease in SOD and GSH-Px activity of serum in 60 mg/kg body weight group. Significant elevations in the mRNA levels of Fas, FasL, calpain-1, cytochrome c, Bax, Bak, and caspase-3, -8, -9, -12 were observed in testis of rat treated with p,p'-DDE. Taken together, these results lead us to speculate that in vivo exposure to p,p'-DDE might induce testicular apoptosis in pubertal rats through the involvement of Fas/FasL, mitochondria and endoplasmic reticulum-mediated pathways.