Tie-2 and angiopoietin-2 expression at the fetal-maternal interface: a receptor ligand model for vascular remodelling

The blood vessels at the fetal-maternal interface widen dramatically during pregnancy in order to increase blood flow to nourish the developing fetus. This vessel remodelling destroys normal vessel integrity and encompasses t he dissolution of vessel muscle and elastic tissue. It also includes the di splacement of endothelial cells by fetal trophoblasts that invade the mater nal arteries of the uterus. Interaction between the endothelial cell recept or, Tie-a, and its recently discovered antagonist ligand, angiopoietin-2 (A ng-2), has been implicated in the loosening of vessel structure. Using Nort hern blot hybridization and RNA in-situ hybridization analysis the expressi on pattern of Tie-2, and Ang-2 in the placenta throughout pregnancy, was in vestigated. We found Ang-2 expressed in the syncytiotrophoblast during the first trimester. In addition to the expected expression of the Tie-2 recept or in both fetal and maternal endothelial cells, we observed Tie-2 expressi on in endovascular invasive trophoblasts. These cells of epithelial origin invade the uterine spiral arteries and acquire endothelial cell properties. The temporal- and lineage-specific pattern of expression of Tie-2 and Ang- 2 suggests that this receptor-ligand pair functions during the critical pha se of development of the fetal vasculature and reworking of the maternal ve ssels during normal placentation.