Major loss occurs during early pregnancy which is the most critical stage for survival of the conceptus (early embryo and associated membranes). Approximately 50% of human conceptions fail during the preimplantation or early implantation stages (Roberts and Lowe, 1975). Embryonic loss has assumed a new significance with the introduction of embryo transfer and other assisted reproduction procedures. In human in vitro fertilization programs only one in five single embryos transferred results in a single pregnancy (Trounson, 1984). Early embryonic death can be caused by a number of factors including: 1) failure of the embryo to produce the appropriate signals responsible for establishment of pregnancy, 2) inappropriate uterine responses to these conceptus signals and/or 3) asynchrony between the signals produced by the developing conceptus and the corresponding responses by the uterus. These recognition processes and the factors which regulate them, on the cellular and molecular level, are not well understood. Our long-term goal is to identify component regulators of maternal recognition of pregnancy and implantation in mammals. We have made significant progress in developing an in vitro implantation model that will facilitate analysis of signal transduction between cells within the uterine compartment. This proposal seeks to further develop the biochemical database that will characterize the response of polarized caprine uterine epithelial (UE) cells to environmental regulatory factors during early pregnancy. We will test the hypothesis that specific carbohydrate epitopes are synthesized and secreted and/or inserted into the apical membrane of UE cells in response to ovarian steroids. Once uterine cellular responses to steroid hormones have been well documented, trophoblastic vessicles will be tested in the in vitro model for their ability to attach to steroid-treated polarized UE cells grown over US. Antagonists and/or potential inhibitors of trophoblast - UE cell adhesion, identified as the result of the studies outlined in this proposal, will then be introduced to further strengthen the concept that specific carbohydrate recognition markers are involved in trophoblast - UE cell adhesion during implantation in mammals.
