MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Toxicol Lett. 2010 Mar 1;193(1):79-85. doi: 10.1016/j.toxlet.2009.12.008. Epub 2009 Dec 16.
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.
1,1-二氯-2,2 双（对氯苯基）乙烯（p,p'-DDE）是 2,2-双（4-氯苯基）-1,1,1-三氯乙烷（DDT）的主要代谢物，是一种已知的持久性有机污染物和雄性生殖毒物。它具有抗雄激素作用。然而，p,p'-DDE 暴露导致雄性生殖毒性的机制尚不清楚。为了阐明 p,p'-DDE 对睾丸影响的机制，我们试图研究 Fas/FasL 凋亡途径在未成年大鼠睾丸中的作用，包括 Fas、FasL、caspase-8、-3 和 NF-κB。动物通过腹腔注射，每隔一天给予不同剂量的 p,p'-DDE（0、20、60、100mg/kg b.wt），连续 10 天。结果表明，p,p'-DDE 暴露剂量超过 20mg/kg b.wt 时，表现出诱导细胞凋亡的作用。p,p'-DDE 可诱导 MDA 水平升高，SOD 和 GSH-Px 活性降低。在 100mg/kg b.wt 组中，Fas 的 mRNA 水平显著升高，同时 FasL、caspase-3、-8 增加。在蛋白质水平上，p,p'-DDE 可诱导 FasL 增加，procaspase-8 减少。NF-κB p65 在 p,p'-DDE 处理的大鼠睾丸中被激活。此外，100mg/kg b.wt 组中 caspase-3、-8 的活性增加。综上所述，这些结果表明，体内暴露于 p,p'-DDE 可能通过 Fas/FasL 途径诱导未成年大鼠睾丸凋亡。
