Establishment of endometrium organoids and application for regenerative medicine of endometrium

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03825
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Sugino Norihiro 山口大学, 大学院医学系研究科, 教授 (10263782)
• Co-Investigator(Kenkyū-buntansha): 田村 功 山口大学, 大学院医学系研究科, 助教 (40610663)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 子宮内膜 / オルガノイド / 着床 / 不妊症 / 再生医療

Outline of Final Research Achievements

We, for the first time, newly developed mouse endometrium organoids including both endometrial epithelial cells and stromal cells. Especially, our endometrium organoids are formed by epithelial cells outside and stromal cells inside, which is similar to the normal endometrium. Furthermore, they can be cultured without any extracellular matrix, such as Matrigel, which allows embryos to access the endometrium organoid in vitro. Therefore, we incubated the newly developed endometrium organoids with mouse blastocysts to observe the implantation process. We confirmed the major four steps during implantation; attachment of blastocysts to the epithelium, invagination of the epithelium, entosis (opening of the epithelium), and invasion of the trophoblasts into the stroma. Our newly developed endometrium organoids are useful models to investigate implantation process in vitro and will provide new insights into recurrent implantation failure.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、最新の手法であるオルガノイド法を利用し、上皮細胞を外側に間質細胞を内側に配置した子宮内膜オルガノイド（ミニ子宮内膜）の作製に世界で初めて成功した。このミニ子宮内膜と胚との共培養によって着床現象の詳細な過程を明らかにすることができ、学術的な意義は大きい。また、子宮内膜の器質的障害を持つ不妊患者に、ミニ子宮内膜を移植することで妊孕性を改善できる可能性を示したものである。子宮性不妊に対する新たな治療法（子宮内膜再生医療）の開発に繋がるものであり、社会的貢献度は大きい。