| Project/Area Number |
17K17918
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
Endocrinology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 卵巣老化 / アルドケト還元酵素 / GONAD法 / 次世代シーケンサー / ゲノム編集 / 次世代シーケンス / 卵胞培養 / 次世代DNAシーケンサー / 卵巣 / 老化 |
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| Outline of Final Research Achievements |
There are various causes in the loss of ovarian function with aging, and many unclear points regarding the molecular mechanism. The purpose of this study was to thoroughly investigate the gene expression of mouse ovaries using a next-generation sequence, to extract a group of genes that markedly change with age, and to clarify their involvement in ovarian function decline. As a result, the gene showing the greatest change was the gene encoding aldoketo reductase, and the expression level of this gene was decreased, and further the enzyme activity was also decreased. When a knockout mouse was created by genome editing to investigate the reproductive function of aldoketo reductase, the estrous cycle was clearly prolonged compared with the wild type. This suggested an abnormal secretion of ovarian hormones that control the estrous cycle, and was considered to be a factor of ovarian function decline with age.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢に伴う卵巣機能の低下は、生殖能力の低下をまねくと同時に、卵巣ホルモン分泌の低下により動脈硬化、骨粗しょう症、認知症といった加齢性疾患のリスク要因となる。分子メカニズムを理解することは、少子化の抑制、健康寿命の推進を実現する上で重要である。本研究は、マウスの加齢卵巣でアルドケト還元酵素遺伝子の発現量・機能が顕著に低下することを明らかにし、その遺伝子欠損マウスは性周期が延長することから、ホルモン代謝の異常が示唆された。よって、この酵素は加齢による卵巣機能低下の要因の一つを担っている可能性がある。今後、卵巣のアンチエイジングを実現する上で重要な成果である。
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