Mechanism of maternal vascular remodeling during human pregnancy

Remodeling of maternal spiral arteries by invasion of extravillous trophoblast (EVT) is crucial for an adequate blood supply to the fetus. EVT cells that migrate through the decidual tissue destroy the arterial muscular lining from the outside (interstitial invasion), and those that migrate along the arterial lumen displace the endothelium from the inside (endovascular invasion). Numerous factors including cytokines/growth factors, chemokines, cell adhesion molecules, extracellular matrix-degrading enzymes, and environmental oxygen have been proposed to stimulate or inhibit the differentiation/invasion of EVT. Nevertheless, it is still difficult to depict overall pictures of the mechanism controlling perivascular and endovascular invasion. Potential factors that direct interstitial trophoblast towards maternal spiral artery are relatively high oxygen tension in the spiral artery, maternal platelets, vascular smooth muscle cells, and Eph/ephrin system. On the other hand, very little is understood about endovascular invasion except for the involvement of endothelial apoptosis in this process. Only small numbers of molecules such as polysialylated neural cell adhesion molecules and CCR1 have been suggested as specific markers for the endovascular trophoblast. Therefore, an initial step to approach the mechanisms for endovascular invasion could be more detailed molecular characterization of the endovascular trophoblast.