2022 Fiscal Year Final Research Report

Exploring meiosis-related factors in patients with primary ovarian insufficiency

Research Project

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Project/Area Number	19K09755
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56040:Obstetrics and gynecology-related
Research Institution	Kumamoto University
Principal Investigator	Itoh Fumiko 熊本大学, 大学院生命科学研究部(医), 特定研究員 (90648271)
Co-Investigator(Kenkyū-buntansha)	石黒啓一郎熊本大学, 発生医学研究所, 教授 (30508114) 大場隆熊本大学, 大学院生命科学研究部(医), 准教授 (50244132) 片渕秀隆熊本大学, 大学院生命科学研究部(医), 名誉教授 (90224451) 小寺千聡熊本大学, 大学院生命科学研究部(医), 研究員 (80879940)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	原発性卵巣不全 / 原発性無月経 / 減数分裂 / 不妊症
Outline of Final Research Achievements	Mutations in meiosis-regulated genes have been postulated as one of the causes of primary ovarian failure. The objectives of this study were (1) to investigate the possibility of genetic abnormalities in StIP1 (=MEIOSIN), a novel factor essential for meiosis initiation in human primary ovarian failure, and in the STRA8-meiosin-regulated gene cluster, and (2) to examine the role of the uncharacterized factor StIP2 in meiosis. In (1), we expanded the scope of analysis to the STRA8-meiosin-regulated gene group based on the results of the parallel basic research. At present, no pathological mutations of the target genes have been identified in patients with primary ovarian failure. We will continue to collect samples, and if candidate mutations are identified, we will generate genetically engineered mice for phenotypic analysis. The StIP2-deficient mice did not show any obvious meiotic abnormalities and fertility abnormalities.
Free Research Field	産婦人科
Academic Significance and Societal Importance of the Research Achievements	本研究は、原発性卵巣不全に至る卵子枯渇の原因を、臨床と基礎の両面からアプローチすることにより解明しようとする研究である。病態が解明されることで、現在は内分泌学的閉経に対するエストロゲン補充や不妊症に対する卵子提供しかない本疾患の根本的治療への発展が期待される。これまでの解析で原発性卵巣不全患者のSTRA8-meiosin制御下遺伝子に病的変異は同定されておらず、今後も検体収集を継続し、候補変異が同定された場合は遺伝子改変マウスを作成し表現型を解析する。