UTERINE RECEPTIVITY TO TROPHOBLAST ADHESION

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The objective of the research proposed is to identify and characterize properties of the rabbit uterine surface which are required for adhesion and fusion with the trophoblastic surface of an implanting embryo. The hypothesis to be tested is that the epithelial surface is the primary site for mediation of hormonally-regulated receptiveness of the uterus, and that apical membranes of opposed trophoblast and uterine cells will adhere via receptor-ligand interactions. Biochemical and structural approaches will be employed to identify components of uterine and trophoblast surfaces which participate in the recognition, adhesion, and fusion events at implantation. Aims of the project include 1) to characterize adhesion interactions between rabbit uterine epithelial cell cultures and trophoblast vesicle preparations and define the effects of steroid hormones and stromal cells on the interaction, 2) to identify functional adhesion components using the trophoblast vesicle-epithelium system assay, 3) to identify plasma membrane polypeptides of receptive uterine epithelium and the trophoblast surface which demonstrate complementary ligand-receptor interaction of potential relevance to implantation, and 4) to characterize the surface components identified in aims 2 and 3 with respect to potential as markers of uterine receptivity and trophoblast differentiation using structural and immunolocalization procedures. Several markers of uterine receptivity in the rabbit have been identified and the in vitro model to be employed offers promise for determining functional adhesive or fusigenic roles for these and for identifying additional adhesive membrane components. The results obtained will add to our understanding of mechanisms underlying the development of a receptive uterus as distinguished from one refractory to implantation.