Embryonic beta-catenin is required for priming of the uterus to implantation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16824
• 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: National Center for Child Health and Development
• Principal Investigator: Iwai Maki 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, リサーチアソシエイト (70645267)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 着床 / 着床不全 / β-カテニン / LIF / CDX2 / サイトカイン / Wntシグナリング / 不妊

Outline of Final Research Achievements

Repeated implantation failure is a major cause of infertility in otherwise healthy women. Uterine beta-catenin (CTNNB1) plays a critical role in the establishment of implantation. However, the role of embryonic CTNNB1 in implantation is unclear. We addressed this issue by analyzing mice carrying Ctnnb1-deficient embryos (Ctnnb1Δ/Δ embryos). Ctnnb1Δ/Δ embryos were produced by intercrossing mice bearing β-catenin-deficient eggs and sperm. Ctnnb1Δ/Δ blastocysts were formed, but embryos were resorbed and empty decidual capsules were formed. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable, and CDX2, a transcription factor determining trophectoderm cell fate, could not be observed in Ctnnb1Δ/Δ blastocysts. Intrauterine injection of uterine fluids from control mice recovered the uterine response to Ctnnb1Δ/Δ blastocysts. These results indicate that uterine response to implantation is inducible by supplemental materials.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

これまで分子生物学的研究や細胞生物学的研究などの研究により、着床や妊娠維持を成功させるために子宮側が起こす反応については解明が進んできた。その一方、着床において胚がどのような役割を持っているのかは未だに不明な点が多い。本研究によってマウスにおける着床に必須な胚側因子を明らかにすることは、着床メカニズムを解明するための第一歩となる。更に、この研究を発展させることにより、不妊の大きな原因の一つである着床不全の解明と治療への助けとなる。