Low estradiol levels in the irst trimester are critical for trophoblast invasion and remodeling of the spiral arteries. nimal studies suggest that the rise in second-trimester estradiol levels suppresses and limits vessel remodeling by reducing trophoblast expression of VEGF and speciic integrin receptors (Bonagura, 2012). Namely, extravillous trophoblasts express integrin receptors that recognize the extracellular matrix proteins collagen IV, laminin, and ibronectin. Binding of these matrix proteins and integrin receptors initiates signls to promote trophoblast cell migration and differentiation. However, as pregnancy advances, rising estradiol levels downregulate VEGF and integrin receptor expression. This represses and controls the extent of uterine vessel transformation.
One of the most remarkable features of human placental development is the extensive modification of maternal vasculature by trophoblasts, which are by definition of fetal origin. These events occur in the first half of pregnancy and are considered in detail because of their importance to uteroplacental blood flow. They are also integral to some pathological conditions such as preeclampsia, fetal-growth restriction, and preterm birth. Spiral artery modiications are carried out by two populations of extravillous trophoblasts-endovascular trophoblasts, which penetrate the spiral-artery lumen, and interstitial trophoblasts, which surround the arteries (see Fig. 5-8).
Interstitial trophoblasts constitute a major portion of the placental bed. They penetrate the decidua and adjacent myometrium and aggregate around spiral arteries. Although less defined, their functions may include vessel preparation for endovascular trophoblast invasion.
Endovascular trophoblasts irst enter the spiral artery lumens and initially form cellular plugs. They then destroy vascular endothelium via an apoptosis mechanism and invade and modiy the vascular media. hus, fibrinoid material replaces smooth muscle and connective tissue of the vessel media. Spiral arteries later regenerate endothelium. Invading endovascular trophoblasts can extend several centimeters along the vessel lumen, and they must migrate against arterial flow. Of note, invasion by trophoblasts involves only the decidual spiral arteries and not decidual veins.
Uteroplacental vessel development proceeds in two waves or stages (Ramsey, 1980). The irst occurs before 12 weeks' postfertilization, and spiral arteries are invaded and modiied up to the border between the decidua and myometrium. he second wave, between 12 and 16 weeks, involves some invasion of the intramyometrial segments of spiral arteries. Remodeling converts narrow-lumen, muscular spiral arteries into dilated, low-resistance uteroplacental vessels. Molecular mechanisms of these crucial events, their regulation by cytokines, signaling pathways, and their significance in the pathogenesis of preeclampsia and fetal-growth restriction has been reviewed by several authors (Pereira de Sousa, 2017; ie, 2016; Zhang, 2016).
Approximately 1 month after conception, maternal blood enters the intervillous space in fountain-like bursts from the spiral arteries. Blood is propelled outside of the maternal vessels and sweeps over and directly bathes the syncytiotrophoblast.