The maintenance of mucosal integrity by adhesion proteins during early pregnancy in the rat

Abstract

In preparation for implantation, uterine luminal epithelial cells (UECs) must perform a dual function of loosening the epithelial barrier to facilitate blastocyst penetration to the stroma, while also producing an intact mucosa to prevent infection. The mechanism of how UECs perform this dual function has not been explored. This thesis aimed to investigate whether specific adhesion proteins that mediate mucosal integrity in other tissues, including Epithelial Cell Adhesion Molecule (EpCAM), tumour necrosis factor , also known as A Disintegrin And Metalloprotease 17 (TACE/ADAM17), claudin 7, nectin-3 and the mucins Muc13 and Muc15, are involved in performing this dual function, as well as their mode of regulation, in UECs during the time of implantation in the rat. The studies in this thesis showed that EpCAM, claudin 7, nectin-3 and Muc13 are either maintained or upregulated at the time of implantation and together, serve to maintain both cellular contacts (EpCAM, claudin 7 and nectin-3) and disseminate anti-apoptotic (Muc13) cues to facilitate mucosal integrity at a critically unstable time when the uterine epithelium is breached during blastocyst implantation. Furthermore, understanding the regulation of these proteins may be important to highlight potential causes of infertility and also potentially develop new avenues for contraceptive targets.