The molecular basis of embryo implantation still remains an area that needs exploration. Species with hemochorial (humans), endothelial (rodents), epithelialchorial (pigs) and synepithelialchorial (ruminants), placentation all must undergo initial adhesion of the trophoblast to uterine epithelial cells. This common event is extremely important as it determines the outcome of placentation and hence a successful pregnancy. The pig is an ideal model to study embryo implantation, because its epithelialchorial placentation involves no invasion of maternal tissues. Thus, initial adhesion events are not confounded by later events of embryo implantation. A diversity of factors has been implicated in playing a role in embryo implantation, but their mechanism of action has remained elusive. Heparan sulfate proteoglycans (HSPG) and their binding proteins have been described as potential players in the process of embryo implantation in rodents and humans. However, the roles of HSPGs and their bindings proteins have not been examined in the pig. A novel protein, Heparin Interacting Protein (HIP), has been cloned from human cell-lines and has been identified and characterized in mice. HIP is a peripheral protein that is expressed in uterine epithelial that it may be directly involved in the initial adhesion event of embryo implantation, facilitating the attachment of the trophoblast to the uterine epithelium. Therefore, this project will explore the potential role of HIP in the initiation of placentation. Studies will be conducted to determine the spatial and temporal expression of HIP in the porcine uterus the spatial and temporal expression of Hip in the porcine uterus during early pregnancy. Further in vitro studies will be performed to establish that HIP is expressed on the apical surfaces of polarized porcine uterine epithelial cells and that steroid hormones module this expression. Evidence would then substantiate the hypothesis that HIP is expressed on the surface of the uterine luminal epithelial during the period of embryo attachment. Moreover, the data will be extremely useful in determining that HIP functions by binding ligands on the trophoblastic epithelial in the initial adhesion event of embryo implantation. This project will provide information on the initial adhesion events in embryo implantation and could therefore lead to improved productive assisted technologies and hence successful pregnancies.
