Shi Yuqin, Song Yang, Wang Yinan, Liang Xianmin, Hu Yafei, Guan Xia, Cheng Jin, Yang Kedi
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, China.
J Biomed Biotechnol. 2009;2009:181282. doi: 10.1155/2009/181282. Epub 2009 Jul 22.
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. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p'-DDE-induced toxicity in male reproductive system. The results indicated that p,p'-DDE exposure at over 30 muM showed the induction of apoptotic cell death. p,p'-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l-cysteine (NAC). In addition, caspase-3 and -8 were activated by p,p'-DDE treatment in these cells. The activation of NF-kappaB was enhanced with the increase of p,p'-DDE dose. Taken together, these results suggested that exposure to p,p'-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway.
1,1-二氯-2,2-双（对氯苯基）乙烯（p,p'-滴滴伊）是2,2-双（4-氯苯基）-1,1,1-三氯乙烷（滴滴涕）的主要代谢产物，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'-滴滴伊暴露导致雄性生殖毒性的机制尚不清楚。在本研究中，使用大鼠支持细胞来研究p,p'-滴滴伊诱导雄性生殖系统毒性的分子机制。结果表明，暴露于超过30μM的p,p'-滴滴伊会诱导凋亡性细胞死亡。p,p'-滴滴伊可诱导FasL mRNA和蛋白增加，这可被抗氧化剂N-乙酰-L-半胱氨酸（NAC）阻断。此外，p,p'-滴滴伊处理可激活这些细胞中的caspase-3和-8。随着p,p'-滴滴伊剂量的增加，NF-κB的激活增强。综上所述，这些结果表明暴露于p,p'-滴滴伊可能通过FasL依赖性途径诱导大鼠支持细胞凋亡。
