Perfluorononanoic acid induces apoptosis involving the Fas death receptor signaling pathway in rat testis.
Perfluorononanoic acid (PFNA, C9), a synthetic perfluorinated chemical containing nine carbons, accumulates and is biomagnified through food webs. This compound has been detected in the serum of humans and wildlife and has the potential for reproductive interference. Few studies, however, have reported the effects of PFNA exposure on male reproduction. To determine this, male rats were orally dosed for 1, 3 and 5mg/kgday PFNA or with vehicle for 14 days. In the present study, serum testosterone levels were decreased, while estradiol levels were increased dramatically in rats receiving 5mg PFNA/kgday. Spermatogenic cells from rats that received 5mg PFNA/kgday exhibited apoptotic features including crescent chromatin condensation and chromatin margination. Flow cytometric analysis and TUNEL assays revealed a dose-dependent increase of apoptotic cell numbers. In addition, expression of Fas and Bax mRNA levels were upregulated significantly, and Bcl-2 mRNA levels were downregulated markedly in the 3 and 5mg/kgday groups. A dose-dependent increase in levels of active caspase-8 and no significant changes of active caspase-9 were observed. Our results indicate that PFNA exposure can lead to cell apoptosis in rat testis, and this apoptosis was probably associated with the Fas death receptor-dependent apoptotic pathway.
Feng
Yixing
Y
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Shi
Zhimin
Z
Fang
Xuemei
X
Xu
Muqi
M
Dai
Jiayin
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D005227:Fatty Acids / Q000633:toxicity*; D005434:Flow Cytometry; D005466:Fluorocarbons; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D053200:Fas-Associated Death Domain Protein; D005227:Fatty Acids; D005466:Fluorocarbons; C101816:perfluoro-n-nonanoic acid; D013739:Testosterone; D004958:Estradiol