Mechanism of tissue regeneration in female reproductive organs

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670733
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: MIYADO Kenji 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, 室長 (60324844)
• Research Collaborator: KAWANO Natsuko 明治大学, 農学部, 講師 (00451691) ; SAITO Hidekazu 国立成育医療研究センター, 周産期診療部 (90125766) ; HAMATANI Toshio 慶應義塾大学, 医学部, 講師 (60265882) ; MIYAMOTO YOshitaka 国立成育医療研究センター, 細胞医療研究部, 研究員 (20425705)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 子宮内膜 / 再生 / マイクロエクソソーム / CD9 / VEGF / エクソソーム / テトラスパニン / 膜融合

Outline of Final Research Achievements

In mammals, the female reproductive tract is remodeled cyclically throughout adult life. Despite the expression of CD9 in the epithelium of the uterus, its role is unclear. Here, we addressed this issue by examining fertilization-competent Cd9-/- mice expressing CD9-GFP in their eggs (Cd9-/-TG). Immunobiochemical analysis demonstrated that CD9 was present in the uterine secretions. Electron microscopic analysis revealed the extracellular matrix-like feature of CD9-containing structures. We also found that the litter size of Cd9-/-TG female mice was significantly reduced after their first birth. Histological analysis revealed severely delayed re-epithelialization of the endometrium both in vitro and in vivo in mice. The quantity of vascular endothelial growth factor-A (VEGF-A) was remarkably reduced in Cd9-/-TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.

Free Research Field

生殖生理学、細胞生物学、脂質生物学