Significance Trophoblast cell invasion and modification of maternal spiral arteries is necessaryto provide a high volume, low pressure maternal blood supply to the developing placenta. Inadequate trophoblast invasion is associated with pregnancies complicated by hypertension and intrauterine fetal growth retardation. Objective The objective of this project is to determine the cellular mechanisms involved in the intravascular migration of trophoblast cells into the spiral arteries and their role in remodeling the arterial wall. Results We have examined the mechanisms by which invasive fetal cytotrophoblast cells adhere to endothelial cells that line uterine arteries, and also the expression of catabolic enzymes by cytotrophoblast cells capable of remodeling uterine arteries. The results of studies of the pattern of platelet-endothelial cell adhesion molecule (PECAM-1) on the trophoblast cells that are responsible for uterine artery modification suggest that PECAM has a prominent role in maintaining adhesion between intra-arterial trophoblast cells and arterial endothelium. Studies focussed on modification of the vessels in early pregnancy showed that the remodelling of the arteries, which involves extensive displacement of maternal endothelium and smooth muscle, is accomplished with little evidence of cell death or loss of integrity of the arteries. The results of studies using trophoblast cells isolated from day 30-40 of pregnancy showed that these cells express the same adhesion molecules as intra-arterial cytotrophoblast in situ. These studies showed that trophoblast cells express vitronectin receptor and PECAM, and the vitronectin receptor functions to mediate adhesion to endothelial cells. Future Directions Immunocytochemical studies will examine additional cell adhesion molecules as well as extracellular matrix molecules in relation to remodeling of the spiral arteries. The in vitro studies will include endothelial cells isolated from endometrial microvasculature, as well as culture of endothelial cells on matrigel-coated bicameral migration chambers to examine mechanisms of cytotrophoblast migration. KEYWORDS placenta, trophoblast, endometrium, immunocytochemistry
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