p,p′-DDE induces testicular apoptosis in prepubertal rats via the Fas/FasL pathway |
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Authors: | Yu-Qin Shi Yu-Ping WangYang Song Hao-Wen LiChang-Jiang Liu Zhi-Gang WuKe-Di Yang |
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Affiliation: | 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, 13 Hangkong Road, Wuhan 430030, Hubei, PR China |
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Abstract: | 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-κB. Animals were administered with different doses of p,p′-DDE (0, 20, 60, 100 mg/kg b.wt) every other day by intraperitoneal injection for 10 days. The results indicated that p,p′-DDE exposure at over 20 mg/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 100 mg/kg b.wt group. In protein level, p,p′-DDE could induce increase of FasL and reduction of procaspase-8. NF-κB p65 was activated by p,p′-DDE treatment in rat testis. In addition, the activities of caspase-3, -8 were increased in 100 mg/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. |
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Keywords: | p,p&prime -DDE Fas/FasL NF-κB Caspase Testis Apoptosis |
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