title: A potential target for organophosphate insecticides leading to spermatotoxicity.
abstract: Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.
authors.affiliation: Department of Occupational and Environmental Health, Graduate School of Medical Sciences, Nagoya City University , Nagoya 467-8601, Japan.
authors.forename: Himiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tomizawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Keisuke
authors.initials: K
authors.lastname: Abe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Noro
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
mesh_terms: D000818:Animals; D004822:Epididymis / Q000187:drug effects; D005278:Fenitrothion / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009943:Organophosphorus Compounds / Q000633:toxicity*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*
chemical_list: D007306:Insecticides; D009943:Organophosphorus Compounds; D005278:Fenitrothion