2023 Fiscal Year Final Research Report

Understanding molecular mechanism behind the oocyte's DNA repair ability of sperm genome damage

Research Project

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Project/Area Number	20H03254
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 44010:Cell biology-related
Research Institution	Kyushu University
Principal Investigator	Ohno Mizuki 九州大学, 医学研究院, 助教 (70380524)
Co-Investigator(Kenkyū-buntansha)	日高京子北九州市立大学, 基盤教育センター, 教授 (00216681) 手島康介九州大学, 理学研究院, 教授 (20447593) 續輝久産業医科大学, 産業生態科学研究所, 訪問研究員 (40155429) 中津可道九州大学, 医学研究院, 准教授 (00207820) 作見邦彦九州大学, 生体防御医学研究所, 准教授 (50211933)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	卵子DNA修復 / 次世代影響 / 精子DNA損傷 / 突然変異 / ゲノム維持
Outline of Final Research Achievements	When fertilization occurs with sperm-bearing DNA damage, the biological outcomes may vary depending on the DNA repair capacity of the oocyte. We analyzed the effects of "sperm oxidative DNA damage" and "oocyte DNA repair ability" on offspring by using several DNA repair pathway-defective female mice and wild-type male mice administered oxidants. A decrease in litter size and infertility was observed only when mothers were Ogg1 knockout and mated with oxidant-treated males. OGG1 is an enzyme involved in base excision repair that specifically removes 8-oxoguanine, an oxidized form of guanine. These findings suggest the importance of OGG1 in post-fertilization repair of oxidative DNA damage induced by sperm DNA.
Free Research Field	分子遺伝学
Academic Significance and Societal Importance of the Research Achievements	本研究の成果は現在のヒトの生殖医療での種々の課題の他、晩婚化に伴う少子化問題、医療放射線被ばくや宇宙環境での長期滞在での生殖細胞保護など、またヒト以外でも、畜産分野での優良種の維持保存や絶滅危惧種の保全など、各分野での重要な課題の解決策を見出す分子基盤になることが見込まれる。基礎生命科学分野においては、生物多様性を創出する生殖細胞変異の役割と意義を考察するための知見が得られることが期待でき、学術的にも社会的にも意義が大きい。