EpCAM is decreased but is still present in uterine epithelial cells during early pregnancy in the rat: potential mechanism for maintenance of mucosal integrity during implantation.

Abstract

The non-receptive uterine luminal epithelium forms a polarised epithelial barrier, protective against potential pathogenic assault from the external environment and invasion by the blastocyst. However, during the window of implantation, the uterine luminal epithelial cells (UECs) transition to a receptive state by dismantling many of their intercellular and cell-matrix adhesions in preparation for epithelial detachment and subsequent blastocyst implantation. The present study investigated the presence and regulation of the intercellular adhesion protein, Epithelial Cell Adhesion Molecule (EpCAM) during early pregnancy in the rat to understand its role in the transition to receptivity. Immunofluorescence and western blotting analysis were used to study EpCAM expression in normal pregnancy, hormone replacement studies and pseudopregnancy. EpCAM was abundantly expressed and localised to the uterine luminal and glandular epithelium during the non-receptive state but decreased to lower but still observable levels around the time of implantation. This decrease was not dependent on ovarian hormones or the blastocyst. Further, EpCAM colocalised with but did not associate with its frequent binding partner, Tumour necrosis factor α (TNFα)-converting enzyme, also known as A Disintegrin And Metalloprotease 17 (TACE/ADAM17), at the time of fertilisation. These results suggest that, prior to implantation, EpCAM mediates intercellular adhesion in the uterine epithelium, but that, during implantation when UECs lose the majority of their intercellular and cell-matrix adhesions, EpCAM levels are decreased but still present for the maintenance of mucosal integrity.