How sperm epigenetic profiles impact on gene expression in the brain of offspring

2020 Fiscal Year Final Research Report

• Project Area: Integrative research toward elucidation of generative brain systems for individuality
• Project/Area Number: 16H06530
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: Tohoku University
• Principal Investigator: Osumi Noriko 東北大学, 医学系研究科, 教授 (00220343)
• Co-Investigator(Kenkyū-buntansha): 原 塑 東北大学, 文学研究科, 准教授 (70463891) ; 沖 真弥 京都大学, 医学研究科, 特定准教授 (90452713)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 父加齢 / 精子形成 / エピジェネティクス / DNAメチル化 / ヒストン修飾 / REST / 神経発生 / 母仔分離超音波発声

Outline of Final Research Achievements

In this project, we focused on paternal aging as an environmental factor that may affect the "individuality" of the next generation. Using genetically homogeneous wild-type mice, we conducted bioinformatics analysis of epigenetic changes that occur during spermatogenesis and the resulting changes in gene expression in the fetal brain of offspring, and found that hypomethylation in sperm leads to alterations in the neurodevelopmental program of the offspring. In addition, we obtained various behavioral data after individual identification, and conducted mathematical analysis based on the data to model that paternal aging causes more "atypical" development in the next generation of mice, resulting in diversification of individuality.

Free Research Field

神経発生学、分子生物学、DOHaD

Academic Significance and Societal Importance of the Research Achievements

少子高齢化が進行する社会において、両親が子どもを持つ年齢の上昇は、少子化の直接の原因となるだけでなく、本研究が示したように、父の加齢もまた次世代の健康や疾病に関わるという意味において非常に重要である。本研究成果は、これまで一般的には卵子の老化ほど広く知られてはいなかったものの、疫学的に繰り返し報告されてきた父加齢の次世代への影響に関して、その分子機構の一端を明らかにしたものである。