Remodeling of the human endometrial epithelium is regulated by laminin and type IV collagen

We investigated the expression and function of laminin and type IV collagen (COL-4) in the human endometrial epithelium throughout the menstrual cycle. Their expression was demonstrated by immunohistochemistry, while cytological analysis of the human endometrial epithelial cell line HHUA cultured on laminin- or COL-4-coated plates provided information on their roles in cell proliferation, structure and apoptosis. Laminin and COL-4 were detected in subepithelial basement membrane-like structures and their expression levels varied throughout the menstrual cycle. Laminin expression was significantly decreased in secretory phase endometrial surface epithelium, while COL-4 expression was significantly decreased in late proliferative phase endometrial epithelium and in vascular endothelium. The morphology of proliferating HHUA cells varied depending on the extracellular matrix component coated on the culture plates. COL-4 strongly inhibited cell proliferation of HHUA cells and enhanced Fas antigen (CD95)-mediated apoptosis, while laminin inhibited Fas-mediated apoptosis. These results indicate that the cyclic expression of laminin and COL-4 in basement membrane-like structures of endometrial epithelium may regulate the endometrial epithelial remodeling and embryo implantation during the menstrual cycle.