Elucidation of blastocyst-derived signals that induce uterine AREG expression

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hirate Yoshikazu 東京医科歯科大学, 統合研究機構, 講師 (70342839)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 着床 / 胚盤胞 / マウス / プロテアーゼ

Outline of Final Research Achievements

Implantation of a blastocyst into the uterus proceeds through communication between the blastocyst and the uterus. However, little is known about the signals released from the blastocyst side and acting on the uterus. In this research project, based on the working hypothesis that a blastocyst-derived protease(s) acts on epithelial sodium channels (ENaC) in the uterine lumenal epithelium to initiate the signaling cascade leading to implantation, we searched for protease genes involved in the activation of ENaC during implantation. The RNA-seq results suggest that Klk7 and Prss8, two of the protease genes whose expression is upregulated in blastocysts, may act as signals for the initiation of implantation.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

胚盤胞が着床に至るには、胚盤胞－子宮間のコミュニケーションが重要と考えられている。着床は胚盤胞と子宮が継続的にコミュニケーションを取りながら進行すると考えられている。本研究成果の学術的意義は、胚盤胞由来の最初期のシグナル、すなわち着床開始シグナルの分子的実体が胚盤胞から分泌されるプロテアーゼであることを明らかにしたことである。社会的意義は、少子化を解決するうえで大きな課題となっている不妊治療の成績向上や、子宮外妊娠などの妊娠異常の解明につながる極めて重要な知見を得たことである。