Development of a therapeutic strategy for female infertility by induction of intrauterine Treg cells by administration of short-chain fatty acids.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09488
• 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: Yamagata University
• Principal Investigator: Kawagoe Jun 山形大学, 医学部, 非常勤講師 (60375342)
• Co-Investigator(Kenkyū-buntansha): 永瀬 智 山形大学, 医学部, 教授 (00292326) ; 太田 剛 山形大学, 医学部, 准教授 (50375341) ; 竹原 功 山形大学, 医学部, 助教 (80642496)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 生殖医療 / 不妊症 / 胚着床 / 制御性T細胞 / 短鎖脂肪酸 / 妊娠

Outline of Final Research Achievements

Immune response suppression by regulatory T cells (Treg cells) plays an important role in the establishment of pregnancy. In this research, we aimed to investigate whether short-chain fatty acids (SCFAs) induce regulatory T cells (Treg cells) in the uterus during pregnancy establishment and to understand the mechanism and effects of SCFAs on pregnancy. Female mice were given different types of short-chain fatty acids and then mated with male mice of different backgrounds. We collected uterus, para-aortic lymph nodes, and serum at 3.5 days post coitum (dpc), the time of embryo implantation, and compared the lymphocyte status in lymph nodes and blood using flow cytometry. We found that the group treated with propionic acid alone showed a significant increase in Treg cells in serum and para-aortic lymph nodes, but no significant changes were observed with other administration methods. However, we did not observe any effect on the establishment of pregnancy.

Free Research Field

生殖医療

Academic Significance and Societal Importance of the Research Achievements

不妊治療の社会的需要の高まりと共に、その治療成績改善も強く求められている。子宮内環境の異常、すなわち、炎症や免疫寛容の異常、微生物環境の異常などが胚着床不全の原因として報告され、その安全な治療法の開発が必要である。我々は、腸内での短鎖脂肪酸が全身の免疫調節に重要な働きをすることに注目し、それが子宮内でも炎症の改善や免疫寛容を誘導し妊孕性改善へ向けた効果を発揮できると考えた。実際、プロピオン酸投与が子宮内環境を反映する所属リンパ節内でTreg細胞の誘導に働くことを明らかにした。これは腸内環境の調節により子宮内環境を改善できる可能性を示し、今後の不妊治療への応用を進める基礎的結果として重要である。