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 5 mg/kg day 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 5 mg PFNA/kg day. Spermatogenic cells from rats that received 5 mg PFNA/kg day 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 5 mg/kg day 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.