2022 Fiscal Year Final Research Report

Roles of cell proliferation and differentiation in the acquisition of uterine receptivity

Research Project

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Project/Area Number	19H03144
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 42040:Laboratory animal science-related
Research Institution	The University of Tokyo
Principal Investigator	Hirota Yasushi 東京大学, 医学部附属病院, 准教授 (40598653)
Co-Investigator(Kenkyū-buntansha)	清水良子慶應義塾大学, 医学部(信濃町), 講師 (30348643) 原口広史東京大学, 医学部附属病院, 届出研究員 (50804506) 金谷真由子東京大学, 医学部附属病院, 届出研究員 (60748862) 松尾光徳東京大学, 医学部附属病院, 特任臨床医 (00823618)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	胚着床 / 子宮内膜 / 細胞増殖能 / プロゲステロン受容体 / STAT3 / 網膜芽細胞腫遺伝子 / 子宮内膜上皮 / 胚浸潤
Outline of Final Research Achievements	The process of embryo implantation consists of three steps: embryo pairing, embryo attachment, and embryo invasion. Cell proliferation of the endometrial epithelium is suppressed during embryo apposition, but the mechanism and the physiological significance remain unclear. Using mouse models, we found that suppression of cell proliferation in the endometrial epithelium during the embryo implantation is regulated by progesterone receptor signaling in the endometrial epithelium, STAT3 signaling in the endometrial stroma, and the cell cycle regulator RB in the endometrial stroma. We also found that the inhibited cell proliferation of the endometrial epithelium governs embryo invasion. Furthermore, we found that the cell proliferation of the human peri-implantation endometrial epithelium is not suppressed in the women with recurrent implantation failure but in the fertile women.
Free Research Field	産婦人科学
Academic Significance and Societal Importance of the Research Achievements	胚移植の反復不成功で定義される着床不全は有効な診断・治療法がほとんど提案されておらず、子宮内でおこる着床は未だブラックボックスのままであり、着床不全の診断・治療法の確立が生殖医療の残された大きな課題であった。本研究では、マウスモデルを用いて着床不全の機序を新たに明らかにし、機序の解明に基づく新規の診断・治療法への応用のための科学的基盤を確立できた。またヒト着床期子宮内膜において細胞増殖能評価がヒトにおける着床能の予測方法として臨床応用できる可能性を示すことができた。