Disease predisposition in offspring based on sperm epigenetic variation.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18627
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kyoto University (2020-2021); Tohoku University (2019)
• Principal Investigator: Kimura Ryuichi 京都大学, 医学研究科, 特定助教 (00781759)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 経世代エピゲノム / DNAメチル化

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.

Free Research Field

発生生物学

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。