2018 Fiscal Year Final Research Report

Alcohol-induced mitophagy in testicular cells-a basic study related to male infertility treatment

Research Project

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Project/Area Number	16K11073
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Urology
Research Institution	Osaka Medical College
Principal Investigator	Eid Nabil 大阪医科大学, 医学部 Anatomy, 講師 Lecturer (50570165)
Co-Investigator(Kenkyū-buntansha)	田中義久大阪医科大学, 医学部, 助教 (20648703) 伊藤裕子大阪医科大学, その他部局等, 功労教授 (40148432)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	Autophagy / Mitophagy / Alcohol / Parkin / Testis / Sertoli cell
Outline of Final Research Achievements	Adult Wistar rats was given a single dose of ethanol intraperitoneally (5mg/kg/bw). The testes and other organs such as liver and spleen were removed and processed. Microscopy revealed enhanced germ cell apoptosis in testes of ethanol-treated rats (ETRs) compared to control group. we found that SCs of ETRs were resistant to apoptosis and showed enhanced expression of autophagy and mitophagy proteins LC3, TFEB, Pan cathepsin PINK1 and Parkin using IHC, IF , immunoelectron microscopy and WB. Enhanced mitophagy in SCs of ETRs was confirmed by electron microscopy and seems to be prosurvival as these cells appeared non-apoptotic. In addition, we observed enhanced mitophagy in liver cells of ETRs. In vitro study confirmed the prosurvival role of autophagy in cultured SCs exposed to ethanol because blocking autophagy BY 3-MA in these cells resulted in decreased cell viability. This indicates that autophagy could be cytoprotective for ETRscs and may have implications for fertility treatment.
Free Research Field	Autophagy
Academic Significance and Societal Importance of the Research Achievements	ETR群のセルトリ細胞におけるオートファジーとマイトファジーはエタノールの毒性による細胞死から細胞を守るメカニズムであることを明らかにした。これらは男性の生殖機能に重要であると考えられる。オートファジーとマイトファジーはETR群のセルトリ細胞において増加しており、エタノールの毒性から細胞が生存するための重要な役割を担っていることが明らかとなった。精巣でマイトファジーを誘導する薬品や天然の産物の開発および発見は、不妊症や脂肪肝などのアルコール摂取と関連した病気の治療のターゲットとなりえる。