The physiological role of CD9 and exosomes in oviducts and uteri

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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.