Disease predisposition in offspring based on sperm epigenetic variation.
| Project/Area Number |
19K18627
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Kyoto University (2020-2021)
Tohoku University (2019) |
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Principal Investigator |
Kimura Ryuichi 京都大学, 医学研究科, 特定助教 (00781759)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 経世代エピゲノム / DNAメチル化 / 精子形成 / 精子低メチル化 / 脱メチル化薬剤 / 精子 / ヒストン修飾 / 精子エピゲノム / 発達障害 |
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| Outline of Research at the Start |
近年、精子のエピゲノムが子孫の疾患素因に寄与する因子として着目されている。父親の 加齢は子どもの神経発達障害や統合失調症などの疾患発症リスクとなることが知られ、加齢による精子エピゲノム変化がその背景にある可能性が指摘されている。本研究では、精子のエピゲノム多様性を評価することを通じて父親の加齢が子孫の疾患素因となる生物学的機構を明らかにすることを目的とする。
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| Outline of Final Research Achievements |
In this study, we attempted to mimic age-related sperm DNA hypomethylation by using DNA demethylating agents to verify that changes in sperm DNA methylation status affect the phenotype of offspring. To this end, we administered DNA demethylating agents to male mice and analyzed the phenotypes of pups obtained by mating with female mice, which revealed that the DNA demethylating agents partially mimicked the effect of male aging on phenotypes of the offspring. On the other hand, the patterns of sperm DNA methylation were not very similar, suggesting that the establishment of hypomethylation of sperm DNA by aging and the induction of DNA demethylation by DNA demethylating agents may occur through different mechanisms.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、精子のエピゲノム状態を変化させると子孫の表現型に影響が生じることが明らかとなった。父親の精子形成過程におけるエピゲノム異常が種々の疾患素因を形成する可能性があり、今後の研究により次世代に影響する疾患の新たな治療法や予防法の開発につながることが期待される。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Paternal age affects offspring via an epigenetic mechanism involving REST/NRSF.2021
Author(s)
Yoshizaki Kaichi, Kimura Ryuichi, Kobayashi Hisato, Oki Shinya, Kikkawa Takako, Mai Lingling, Koike Kohei, Mochizumi Kentaro, Inada Hitoshi, Matsui Yasuhisa, Kono Tomohiro, Osumi Noriko
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Journal Title
EMBO Reports
Volume: 22(2)
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Paternal aging affects to phenotypes of offspring through inheritance of hypomethylated DNA elicited in NRSF/REST binding site2019
Author(s)
Kimura R., Yoshizaki K., Kikkawa T., Mai L., Oki S., Mochizuki K., Kobayashi H., Inada H., Matsui Y., Kono T., Osumi N.
Organizer
14th Asia Epigenome Meeting (AEM) / 3rd Taipei Epigenetics and Chromatin Meeting (TECM)
Related Report
Int'l Joint Research
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[Presentation] Paternal aging affects to offspring’s behavior and gene expression possibly through inheritance of hypomethylated DNA elicited in NRSF/REST binding site2019
Author(s)
Kimura R., Yoshizaki K., Kikkawa T., Mai L., Oki S., Mochizuki K., Kobayashi H., Inada H., Matsui Y., Kono T., Osumi N.
Organizer
International Symposium on Epigenome 2019
Related Report
Int'l Joint Research
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