The objective of this project is to determine the cellular mechanisms involved in the intravascular migration of trophoblast cells into the maternal spiral arteries and their role in modeling the arterial wall. Adequate invasion and remodeling of the arteries appears necessary to provide a high volume, low pressure blood supply to the developing placenta. Inadequate arterial invasion has been associated with pregnancies complicated by hypertension and intrauterine growth retardation. During the past year we have begun to identify some of the cell adhesion molecules expressed during trophoblast invasion of the vascular wall. We have identified neural cell adhesion molecule (NCAM) as one class of adhesion molecules that it expressed very early in invasion. It is present only on trophoblast of the shell and on the surface of trophoblast cells invading the arteries. Interestingly, once the trophoblast cells have invaded the wall of the vessel, expression of NCAM is drastically reduced. We have also set up an in vitro cell adhesion assay to study adhesion of isolated trophoblast cells to monolayers of endothelial cells. Blocking antibodies to several adhesion molecules (e.g. endoglin, '1 integrin) significantly reduced adhesion, while antibodies to others (e.g. ICAM-1, P-, L- and E-selectin) did not significantly affect adhesion. These studies are continuing with antibodies to other cell adhesion molecules. This system was used initially with human trophoblast cells, but is now being expanded to macaque trophoblast and endothelial cells. We have also identified the distribution of some extracellular matrix molecules, especially chondroitin sulfate, hyaluronic acid, fibrillin, collagens, in the developing macaque placenta. The localization of these molecules is being analysed in relation to spiral arteries and other endometrial/placental tissues. *KEY* Placenta, Trophoblast, Endometrium, Immunocytochemistry
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