Elucidation of FXR function in the ovary

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05940
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: Shinshu University
• Principal Investigator: Tomioka Ikuo 信州大学, 学術研究院農学系, 准教授 (30528196)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: FXR / 性ホルモン / ノックアウトマウス

Outline of Final Research Achievements

FXR mainly existed in metabolic organs and regulates the cholesterol, lipid, and the glucose homeostasis. FXR had been revealed to be expressing in the ovary. However, the functions and the precise molecular mechanism of FXR in ovary remain still unknown. In this study, we investigated the functions of FXR and its target genes in the ovarian granulosa cells.
To elucidate the function of FXR in the ovary, we generated FXR knockout (FXR-KO) mice using gene editing technology and performed phenotypic analysis. The results showed that FXR-KO female mice had significantly higher ovulation number, blood estradiol concentration, and gene expression of estradiol synthesis-related enzymes in granulosa cells than wild-type mice, suggesting that FXR suppresses ovulation number by repressing and regulating genes involved in sex hormone synthesis.

Free Research Field

動物生殖学

Academic Significance and Societal Importance of the Research Achievements

本研究成果より、FXRは性ホルモン合成に関与する遺伝子群を抑制し、排卵数を抑えている可能性が示された。これまで生殖機能に関与しないとして知られていたFXRであるが、独自に作製したFXR-KOマウスの知見から、FXRは性ホルモン合成に大きく関与していることが示された。食から始まる代謝シグナルと生殖現象は密接に関連しており、その仲介因子がFXRであることを証明できれば、卵胞発育や排卵メカニズムの解明といった基礎研究にとどまらず、卵巣関連疾患の新たな治療法開発に繋がる可能性がある。