Development of treatment and pathogenesis of implantation failure with a focus on the uterine cavity humoral factor

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CD9 is a 24-kD membrane protein, which is localized on endosomes and exosomes as well as cell membranes. Cd9-deficient mouse eggs are unable to fuse with sperm. In this study, we intended that we focused on CD9 of the uterine cavity, and to clarify the role of CD9 in the endometrium. In transgenic mice that were rescued only CD9 expression in the zona pellucida (CD9-/-TG), endometrium of postpartum were not covered with the epithelium, were found extensive adhesions. After measurement of the humoral factors of the uterus cavity fluid, VEGF was decreased in CD9-/-TG compared with wild-type mice, so it was thought that loss of CD9 might interfere with VEGF production. When VEGF was injected in the uterine cavity of CD9 knockout mice, the endometrium was re-epithelialization. CD9 contributed to secretion of VEGF from endometrial epithelial cells, and these results provided the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.