Establishment of uterine bioengineering technology for reproductive medicine

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16022
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: The University of Tokyo (2021); Kitasato University (2019-2020)
• Principal Investigator: Hiraoka Takehiro 東京大学, 医学部附属病院, 助教 (20836762)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: STAT3 / 着床 / 子宮腺筋症 / 子宮再生医療

Outline of Final Research Achievements

The applicant has determined a physiological regulatory mechanism of embryo implantation in the endometrium orchestrated by differential roles of epithelial and stromal STAT3.This result suggests that both epithelial and stromal STAT3 are indispensable for endometrial regeneration and embryo implantation. Moreover, the applicant has established a mouse model of adenomyosis associated with female infertility and represented by ectopic growth of the endometrium in the myometrium. This achievement demonstrated that the endometrium can be reconstructed not only in the normal endometrial extracellular matrix but also in an alternative scaffold. The analysis of genetically modified mouse lacking uterine STAT3 and human specimen showed that the etiology of adenomyosis is critically related to the overactivation of STAT3 in the uterus. These findings will provide a clue to the establishment of in vitro reconstitution of the functional endometrium for epoch-making reproductive treatment.

Free Research Field

生殖医学

Academic Significance and Societal Importance of the Research Achievements

不妊症の原因は多岐にわたるが、着床障害の機序や治療法については未解明な点が多い。本研究は、着床の過程における子宮内膜の分子制御機構を明らかにしたと同時に、不妊症の原因となる子宮腺筋症の病態解明につながるマウスモデルを樹立した。また、これら一連の現象に、子宮再生に必須のSTAT3が密接に関わっていることが明らかとなった。これらの研究成果は、着床障害の原因解明につながるだけでなく、機能的な子宮内膜を試験管内で再構築し生体内に移植する、といった画期的な不妊治療の樹立につながる可能性があり、日本の少子高齢化に対する解決策の一つとなり得る。