Identification of infertile genes in aging mice using genome editing method

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K11128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Yamaguchi University
• Principal Investigator: Mizukami Yoichi 山口大学, 大学研究推進機構, 教授 (80274158)
• Co-Investigator(Kenkyū-buntansha): 大塚 正人 東海大学, 医学部, 教授 (90372945)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 不妊 / 老化 / 全遺伝子解析 / ゲノム編集マウス

Outline of Final Research Achievements

The declining birth rates and aging population is occurring in advanced countries, including Japan, leading to an increase in late childbirth. Despite having eggs in their ovaries, elderly women are experiencing infertility, and understanding the mechanisms of ovulation disorders caused by aging is essential for addressing infertility. We discovered that the oxidative stress response pathway, activated during the early phase of the ovulation hormone response, is significantly reduced by analyzing the whole gene expression in the ovaries of aged mice at each sexual cycle. Based on this data, they conducted ovarian cell profiling analysis in aging mice and elucidated the genes and cells responsible for ovulation disorders. GONAD method, which enables simple generation of knockout mice through genome editing was used, and they clarified the mechanisms of ovulation disorders caused by aging.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

世界の先進国では少子高齢化が進行し、このため労働力不足を補うため、女性が社会進出し、晩婚化・不妊症の増加を招き、労働力人口は負のスパイラルに陥っている。女性の卵巣に存在する卵子は、出生前に造られ、高齢でも卵子（原始卵胞）は卵巣に存在しており排卵機能の制御によって高齢出産は可能である。実際に世界大戦直後の日本では50歳代で数千人が出産していた。卵巣の老化シグナル経路を分子レベルで解明し、排卵シグナル経路を回復することで理論上、卵巣に卵子が存在している限り100歳を越える高齢でも妊娠が可能である。