2017 Fiscal Year Research-status Report
アルコールは精巣の細胞にMitophagyを誘導する―男性不妊治療の基礎的研究―
| Project/Area Number |
16K11073
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| Research Institution | Osaka Medical College |
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Principal Investigator |
Eid NabilA.S. 大阪医科大学, 医学部, 講師 (50570165)
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| 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)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | アルコール / 男性不妊 / セルトリ細胞 / ミトファジー |
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| Outline of Annual Research Achievements |
Ethanol-induced mitophagy in Sertoli cells was investigated in vivo and in vitro. A single administration of 5g/kg ethanol to adult rats enhanced germ cell apoptosis (using TUNEL method and TEM) and mitophagy in Sertoli cells within 24h, compared to control group (injected with PBS). Upregulation of autophagy proteins LC3, pan cathepsin and LAMP-2 was mainly observed in Sertoli cells of ethanol-treated rats (ETRs)using Western blot and immunohistochemical techniques. In addition, enhanced formation of mitophagic vacuoles (autophagic vacuoles containing damaged mitochondria) were observed in Sertoli cells of ETRs using TEM, and these cells appeared normal. Immunohistochemistry and Western blot showed the upregulation of specific mitophagy proteins PINK1and Parkin in Sertoli cells of ETRs. In vitro studies of cultured TM4 Sertoli cells confirmed the upregulation of autophagy protein LC3 on exposure to ethanol. Blocking autophagy in untreated and ethanol-treated cultured Sertoli cells reduced their viability, indicating the cytoprotective role of autophagy against ethanol; which may be important for male fertility.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
アルコールによる障害をまず、セルトリ細胞はオートファジー（ミトファジー）によって回避しているが、障害が長時間に及ぶとアポトーシスで死に陥ることの証明ができているから。
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| Strategy for Future Research Activity |
Because autophagy and mitophagy are important for survival of Sertoli cells (as we found increased Sertoli cell apoptosis on blocking autophagy by 3-MA in vitro study) and supply of lactate to germ cells (via reverse Warburg-like effect), stimulation of autophagy and mitophagy in vivo by rapamycin may enhance the survival of Sertoli cells and the production of essential lactate for germ cells; thus helping infertility associated with germ cell loss or damage induced by ethanol.
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| Causes of Carryover |
ラットにオートファジー阻害剤を投与するin vivoの実験を行っていないため。
複数のラットに投与する阻害剤は高価である。
また、複数の論文を投稿予定であるので、校正料、投稿料が必要であるため。
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Research Products
(4 results)
