| Project/Area Number |
16H05017
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Animal production science
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
星野 由美 広島大学, 生物圏科学研究科, 助教 (10451551)
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| Research Collaborator |
Richards JoAnne S.
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 卵巣 / エピゲノム / 顆粒層細胞 / 遺伝子発現 / クロマチン構造 / 卵胞発育 / DNAメチル化 / エピジェネティクス制御 / 応用動物 / メチル化 / 妊孕性 / エピジェネティクス / 繁殖障害 / 家畜繁殖 / 卵巣機能 |
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| Outline of Final Research Achievements |
During follicular development process in ovary, about 30% of genome were demethylated in granulosa cells. The demethylation was dependent on cell proliferation and de-novo synthesized retinoic acid. The DNA demethylation switched on the acetylation of histone H3, which changed the morphology of chromatin to open chromatin status. The granulosa cell proliferation that was essential for DNA demethylation was not observed in aged ovary where fibrosis was grown in ovarian stroma. Additionally, we also cleared that the increase of mitochondria activity was required for the cell proliferation in granulosa cells.
This basic information about the molecular mechanisms of follicular development will be contributed for understanding reproductive disorder with increasing age, by inadequate nutrients and by infection and so on. These understandings lead to develop the clinical care to improve infertility.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢に伴う妊孕性の低下，感染症や低栄養条件による繁殖障害が家畜やヒトで問題となっている．本研究で明らかとした卵胞発育の分子生物学的理解は，上記が起こる根本原因を解き明かす第一歩となる．
本研究で明らかとなった，レチノイン酸がDNA脱メチル化誘導因子であることや細胞増殖のためにミトコンドリアの活性化が必須であるとの知見は，食事（飼養環境）が卵巣機能に直結することを示す研究成果であり，このような知見が繁殖障害や不妊症の予防法開発や治療法の発見につながると期待できる．
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