| Project/Area Number |
24659303
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene
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| Research Institution | Tokyo University of Agriculture (2013)
Nagoya City University (2012) |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KAMIJIMA Michihiro 名古屋市立大学, 大学院医学研究科, 教授 (80281070)
ITO Yuki 名古屋市立大学, 大学院医学研究科, 講師 (80452192)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 環境保健 / 農薬 / 毒性 / 殺虫剤 / 精子毒性 / 生殖毒性 |
|---|
| Research Abstract |
Organophosphate (OP) insecticides also act on the diverse serine hydrolase targets, thereby revealing unexpected toxic effects including male reproductive toxicity. The present investigation detects a target molecule for OP-induced spermatotoxicity. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the OP target in the rodent testicular membrane proteome, i.e., OP phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, rodents were treated with vehicle or OP compounds (10 days or 9 weeks), and FAAH activity in testis or epididymis cauda was reduced by the treatments. ABPP analysis revealed that FAAH was selectively inhibited among the OP-treated testicular proteome. The FAAH substrate anandamide levels were elevated by the OP treatments. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.
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