| Project/Area Number |
17K16844
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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 |
Obstetrics and gynecology
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| Research Institution | Nagoya University |
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Principal Investigator |
Osuka Satoko 名古屋大学, 医学部附属病院, 講師 (30778296)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 多嚢胞性卵巣症候群 / エピジェネティック変化 / エピジェネティクス / モデル動物 / メチル化変異 / 卵子メチル化 / 胎児環境 |
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| Outline of Final Research Achievements |
To find the new therapeutic target of PCOS, we conducted experiments with rat models of PCOS.Hypothalamus and livers were analyzed for differentially expressed genes (DEGs) using RNA-Seq, and DNA methylation were analyzed using MBD (Methyl-CpG-binding domain) -seq methods. DNA methylation analysis showed 424 hypomethylated and 500 hypermethylated promoter regions in the hypothalamus, 186 hypomethylated and 200 hypermethylated promoter regions in the liver of the PCOS models. RNA-seq revealed that 12 DEGs in the hypothalamus and 47 DEGs in the liver (|Fold change|>2, P<0.05) of the PCOS models. In these genes, Vgut1 showed hypermethylated status of promoter resion and down-regulated expression in the hypothalamus, Bcmo1 showed hypomethylated status in promoter region and down-regulated expression in the liver. Some genes coding hepatokines including Lect2 and Rbp4 were upregulated in the livers.These molecules could be expected to be the therapeutic target for PCOS.
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| Academic Significance and Societal Importance of the Research Achievements |
PCOSは、不妊症のみでなく、2型糖尿病、高脂血症などの代謝異常や、子宮体がん、さらには妊娠高血圧腎症、妊娠糖尿病などの周産期合併症の増加に関連するが、病因の詳細は不明である。PCOSの基本症状は、多嚢胞性卵巣、排卵障害、無月経、高アンドロゲン血症、下垂体ゴナドトロピン分泌異常であり、これらに着目した病態の解析や対症療法が行われてきた。しかし、本疾患の根本的な治療法の開発には至っていない。今回は、複数臓器のエピジェネティック変化に着目した解析により、新規治療標的候補を同定した。これらを対象とした治療法開発により、不妊症のみならず、女性のQOL向上に役立つ可能性がある。
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