p,p'-DDE induces testicular apoptosis in prepubertal rats via the Fas/FasL pathway

Abstract

1,1-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 Fas/FasL apoptotic pathway in the testis of prepubertal rats, including Fas, FasL, caspase-8, -3, and NF-kappaB. Animals were administered with different doses of p,p'-DDE (0, 20, 60, 100mg/kg b.wt) every other day by intraperitoneal injection for 10 days. The results indicated that p,p'-DDE exposure at over 20mg/kg b.wt showed the induction of apoptotic cell death. p,p'-DDE could induce increase in the MDA level, and decrease in SOD and GSH-Px activity. Significant elevations in the mRNA levels of Fas along with an increase in FasL, caspase-3, -8 were observed in 100mg/kg b.wt group. In protein level, p,p'-DDE could induce increase of FasL and reduction of procaspase-8. NF-kappaB p65 was activated by p,p'-DDE treatment in rat testis. In addition, the activities of caspase-3, -8 were increased in 100mg/kg b.wt group. Taken together, these results lead us to speculate that in vivo exposure to p,p'-DDE might induce testicular apoptosis in prepubertal rats through the Fas/FasL pathway.