A Potential Target for Organophosphate Insecticides Leading to Spermatotoxicity
| Autor: | Michihiro Kamijima, Yuki Ito, Motohiro Tomizawa, Yuki Noro, Himiko Suzuki, Keisuke Abe |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Insecticides Motility Biology Mice chemistry.chemical_compound Organophosphorus Compounds Fatty acid amide hydrolase Testis medicine Animals Sperm motility Epididymis Mice Inbred ICR Oxon Organophosphate Serine hydrolase Fenitrothion General Chemistry Spermatozoa medicine.anatomical_structure Biochemistry chemistry Sperm Motility General Agricultural and Biological Sciences Reproductive toxicity |
| Zdroj: | Journal of Agricultural and Food Chemistry. 61:9961-9965 |
| ISSN: | 1520-5118 0021-8561 |
| DOI: | 10.1021/jf4033365 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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