Spiral artery remodeling in normal pregnancy and preeclampsia

(A) Schematic of normal and pathological remodeling in the pregnant uterus. The process occurs in the first trimester and early second trimester. The vessel on the left shows a normal spiral artery, replete with full endothelial cell and vascular smooth muscle cell lining, prior to being remodeled. Blood flow returns via a uterine vein (not shown). The vessel in the middle shows a fully remodeled spiral artery. The remodeled vessel has lost its smooth muscle cell lining, and its endothelial cells have been replaced by extravillous trophoblasts (EVTs) that had migrated out from anchoring placental villi into the decidua. The remodeling process extends all the way through the decidua and into the superficial layers of the myometrium, thus greatly reducing vascular resistance and increasing blood flow to the placenta. Decidual natural killer (dNK) cells, which aggregate at areas of ongoing remodeling, are also depicted. EVTs also invade into the uterine veins, thus providing an outlet for placental blood flow (not shown). The vessel on the right is a poorly remodeled spiral artery. It retains much of its own endothelial cell and vascular smooth muscle cell lining, and EVT invasion does not reach the myometrium. As a result, blood flow to the placenta is insufficient to meet the demands of the growing conceptus, which is thought to lead to preeclampsia, intrauterine growth restriction, and other maternal and fetal pathologies in the third trimester. Poor spiral artery remodeling is associated with inadequate dNK cell activation. In mice, the spiral arteries similarly lose their vascular smooth muscle cell lining, which by itself increases blood flow, but trophoblast invasion into the vessels is normally "shallow" and restricted to the decidua.