p,p'-DDE induces apoptosis of rat Sertoli cells via a FasL-dependent pathway.
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.
Shi
Yuqin
Y
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.
Song
Yang
Y
Wang
Yinan
Y
Liang
Xianmin
X
Hu
Yafei
Y
Guan
Xia
X
Cheng
Jin
J
Yang
Kedi
K
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D053222:Fas Ligand Protein / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects
D017302:Annexins; D053222:Fas Ligand Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D011419:Propidium; D003633:Dichlorodiphenyl Dichloroethylene; D053148:Caspase 3; D053181:Caspase 8; D000111:Acetylcysteine