Interplay between epigenetics and metabolism in transgenerational inheritance

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02383
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Maezawa So 東京理科大学, 創域理工学部生命生物科学科, 准教授 (90548174)
• Co-Investigator(Kenkyū-buntansha): 林 陽平 東北大学, 加齢医学研究所, 助教 (00588056) ; 大我 政敏 麻布大学, 獣医学部, 講師 (40644886)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 精子形成 / エピジェネティクス / 代謝 / 生殖細胞

Outline of Final Research Achievements

A father’s diet can have a significant effect on the future health of his offspring. Although metabolites in spermatogenesis can alter the epigenome in sperm, it remains unclear what and how the nutrient condition affects the germline epigenome established in spermatogenesis. Here we aimed to understand the metabolome dynamics in spermatogenesis. We conducted integrated transcriptomic, proteomic, and metabolomic analyses of male germ cells in mouse spermatogenesis and demonstrated differentiation stage-dependent changes in these processes. We observed that SGOC pathway is consistently upregulated in spermatogonia and spermatocytes, suggesting their involvement in epigenetic changes preceding in males. We further demonstrated that SGOC is important for the progression of spermatogenesis through the establishment of H3K4me1. Our findings shed light on the unrevealed mechanisms of the metabolism-epigenome crosstalk in spermatogenesis.

Free Research Field

生殖科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、マウス精子形成期において代謝状態が変化すること、さらに代謝状態がエピゲノム形成へ影響を与えることを見出した。今後、精子形成を司る代謝調節システムや、代謝産物がエピゲノム制御に与える分子機構を明らかにすることにより、精子形成に重要な栄養環境の解明に繋がり、将来的に生体外精子形成技術などの再生医学への貢献が期待される。