Identification of cytotoxic factors for eggs and development of neutralizing drugs

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293363
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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)
• Co-Investigator(Kenkyū-buntansha): 河野 菜摘子 明治大学, 農学部, 講師 (00451691)
• Co-Investigator(Renkei-kenkyūsha): INOUE Naokazu 福島県立医科大学, 医学部, 准教授 (90125766) ; SAITO Hidekazu 国立成育医療研究センター, 母性医療診断部, 医長 (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: 卵 / 受精 / 膜融合 / リン脂質 / CD9 / マイクロエクソソーム / エクソソーム / 細胞毒性

Outline of Final Research Achievements

Since CD9 is involved in sperm-egg fusion, this protein may organize membrane architectures. Immunoelectron microscopic analysis revealed that CD9 is incorporated into microexosomes. Since microexosomes have no overt lipid bilayers and seem to be small units, less than 5 nm in diameter, they are structurally different from exosomes. Furthermore, Cd9-deficient eggs could not fuse with sperm, but in the presence of wild-type eggs, 70% of the Cd9-deficient eggs fused with the sperm. Notably, the microexosomes rendered sperm fusion competent with Cd9-deficient eggs, which means that microexosomes, but not the egg microvilli, are essential for sperm-egg fusion. In addition, microexosomes are observed inside the uterus. Taken together, these results indicate that there are two forms of tetraspanin, namely the intercellular transportation-related forms and membrane fusion-related forms.

Free Research Field

生殖生理学、細胞生物学、脂質生物学