Regulation of oogenesis by the unique metabolic status in fetal germ cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03231
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Tohoku University
• Principal Investigator: Matsui Yasuhisa 東北大学, 加齢医学研究所, 教授 (40241575)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 卵母細胞 / 代謝 / エピゲノム / MPC / TCA回路

Outline of Final Research Achievements

This study aimed to show roles of energy metabolism in fetal mouse germ cells for oogenesis. We demonstrated that MPC2, a pyruvate carrier protein on mitochondrial membrane, and α-ketoglutarate in TCA cycle are crucial for early steps of oogenesis by using organ culture of fetal ovary and germ cell-specific knock-out mouse of Mpc2. In addition, we also found that GDF9, an essential factor for oogenesis, is under the control of MPC2, and acetylation of histone H4 in Nobox gene, another essential gene for oogenesis, and its expression are also controlled by MPC2. The results suggest that MPC2 is crucial for gene expression required during oogenesis by the histone modification via α-ketoglutarate.

Free Research Field

Developmental Biology

Academic Significance and Societal Importance of the Research Achievements

本研究により、ミトコンドリア代謝がエピジェネティック制御を介して、卵胞形成に重要な役割を果たす分子機構の一端が、初めて明らかになり、代謝-エピゲノム制御軸による卵子形成制御の新たなしくみを示した。この研究成果は、卵胞形成不全等の疾患の原因の１つとして、ミトコンドリア代謝を介したエピジェネティック異常が関与する可能性を示唆し、今後、Mpc2遺伝子変異の有無による不妊リスクの評価などの発展が期待できる。