p,p'-DDE induces testicular apoptosis in prepubertal rats via the Fas/FasL pathway.
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.
Shi
Yu-Qin
YQ
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.
Wang
Yu-Ping
YP
Song
Yang
Y
Li
Hao-Wen
HW
Liu
Chang-Jiang
CJ
Wu
Zhi-Gang
ZG
Yang
Ke-Di
KD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D053222:Fas Ligand Protein / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation; D015398:Signal Transduction / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000473:pathology*
D053222:Fas Ligand Protein; D007306:Insecticides; D016328:NF-kappa B; D003633:Dichlorodiphenyl Dichloroethylene; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D053181:Caspase 8