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 430030, People's Republic China.
Environ Toxicol. 2013 Jan;28(1):31-41. doi: 10.1002/tox.20694. Epub 2011 Mar 7.
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.
一种名为 1,1-二氯-2,2 双（对氯苯基）乙烯（p,p'-DDE）的物质，是 2,2-双（4-氯苯基）-1,1,1-三氯乙烷（DDT）的主要代谢产物，属于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确切机制尚不清楚。为了阐明 p,p'-DDE 对睾丸影响的机制，我们试图研究青春期大鼠睾丸中凋亡相关基因的 mRNA 表达和凋亡效应，这些基因包括 Fas、FasL、钙蛋白酶-1、细胞色素 c、Bax、Bcl-w、Bak 和 caspase-3、-8、-9、-12。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 体重），连续 10 天。结果表明，p,p'-DDE 暴露剂量超过 20mg/kg 体重时，会诱导细胞凋亡。p,p'-DDE 可诱导 60mg/kg 体重组血清中超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低。用 p,p'-DDE 处理的大鼠睾丸中 Fas、FasL、钙蛋白酶-1、细胞色素 c、Bax、Bak 和 caspase-3、-8、-9、-12 的 mRNA 水平显著升高。综上所述，这些结果使我们推测，体内暴露于 p,p'-DDE 可能通过 Fas/FasL、线粒体和内质网介导的途径诱导青春期大鼠睾丸细胞凋亡。
