Establishment of in vitro oogenesis with high integrity

2022 Fiscal Year Final Research Report

• Project Area: Ensuring integrity in gametogenesis
• Project/Area Number: 18H05547
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: Obata Yayoi 東京農業大学, 生命科学部, 教授 (70312907)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: 卵子 / 卵子形成過程 / 卵胞形成過程 / 発生能 / in vitro

Outline of Final Research Achievements

This study aimed to develop an in vitro system to produce oocytes that achieves high integrity from primordial germ cells. Excessive activation of estrogen signaling in vitro-derived ovaries led to premature expression of AMH, resulting in abnormal follicle formation. On the other hand, the addition of AFP, which is secreted from fetal liver, to the culture medium suppressed estrogen signaling and resulted in normal follicle formation. Furthermore, lowering the concentration of oxygen from 20 to 7% during follicle culture improved abnormal lipid metabolism, restored mitochondrial activity, and improved post-fertilization development in the oocytes. The combination of this in vitro system and the exogenous transfection method via virus vector was shown to rescue oogenesis in congenitally infertile female mice. Thus, mouse oocytes that achieves high integrity were successfully produced in vitro.

Free Research Field

発生工学

Academic Significance and Societal Importance of the Research Achievements

始原生殖細胞（PGC）から卵子を産生するin vitro系の開発は卵子形成機構解明のツールとして有用なばかりでなく、多能生幹細胞から作られる始原生殖細胞様細胞（PGCLC）をもとに成熟卵子を量産させる可能性を秘めている。本研究ではin vitro系を開発する過程で、機能的な成熟卵子の産生に不可欠な卵胞構造の形成に必要な因子が明らかにされた。早発卵巣不全は、世界の40歳未満の女性の1%が罹患しており、女性の不妊症の主要因で早期に卵胞が枯渇することによる。卵胞の形成機構の理解はこうした不妊のメカニズムの解明や治療法の開発に役立つ可能性がある。