Elucidation of the mechanism of differentiation from iPS cells to mural tubules: Toward the creation of new infertility treatment methods

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16768
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Mie University
• Principal Investigator: Takeuchi Hiroki 三重大学, 医学系研究科, 助教 (50739612)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 生殖医療 / 再生医療 / ミュラー管上皮細胞 / 体腔上皮細胞 / 中間中胚葉細胞

Outline of Final Research Achievements

Infertility treatment is an urgent issue in Japan where the birthrate is declining and the population is aging, but the cure for endometrial insufficiency remains poorly improved. With the aim of developing a new treatment method for infertility derived from female reproductive organs among the infertility factors, we attempted to develop an deferentiation method from pluripotent stem cells to Muellerian epithelial cells which are important for early development of female reproductive organs. Although the details of the deferentiation of mueller duct are unknown, We focused on the BMP signaling and retinoic acid pathways and investigated their importance. We demopnstrated that the activation of FGF signal pathway and retinoic acid pathway and inhibition of BMP signaling pathway are important in the differentiation of mesodermal - coelomic epithelial cells -Mullerian epithelial cells.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまでミュラー管の詳細な発生機序は不明であったが、本課題においてミュラー管上皮細胞の発生・誘導には、FGFシグナル経路とレチノイン酸経路の活性化に加え、BMP経路の阻害が重要である事を実証した。これらの発見は、更なる機序解明のための重要な知見となり学術的意義は大きいと考えられる。また不妊治療において過去20年であまり改善していない妊娠率を向上させるため、技術開発のための研究ツールを提供するだけでなく、移植細胞療法や再生医療などへの応用も期待でき、社会的な意義も大きいと考えられる。