title: Fenvalerate induces germ cell apoptosis in mouse testes through the Fas/FasL signaling pathway.
abstract: Fenvalerate has a potentially adverse effect on male reproduction and spermatogenesis, whereas the precise mechanism remains obscure. The present study investigated the effects of fenvalerate on germ cell apoptosis in testes. Adult male mice were administered with fenvalerate (15 or 60 mg/kg) by gavage for 28 days. Germ cell apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). The number of TUNEL+ germ cells per tubule and the percentage of tubules with TUNEL+ germ cells were significantly increased in testes of mice treated with fenvalerate in a dose-dependent manner. TUNEL+ germ cells were observed mainly in stages VII-VIII and also stages IX-XII seminiferous tubules in testes. Additional experiments showed that fenvalerate increased the level of active caspase-8 and caspase-3 in testes. In addition, fenvalerate upregulated the expression of Fas and FasL in testes. No significant difference on the expression of Bcl-2 and Bax in testes was observed between fenvalerate-treated mice and controls. Fenvalerate did not affect the leakage of cytochrome c from mitochondria into cytoplasm. In addition, fenvalerate did not cause the activation of caspase-9 in testes. Taken together, these results suggest that fenvalerate induces germ cell apoptosis in testes through the Fas/FasL signaling pathway.
authors.affiliation: Department of Toxicology, Anhui Medical University, 230032, Hefei, China.
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Zhao
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Ji
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053222:Fas Ligand Protein / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D019014:fas Receptor; C017690:fenvalerate