Abstract
During pregnancy, extensive hemostatic changes occur in the uteroplacental circulation. Invading endovascular trophoblast cells induce physiological adaptations of uterine spiral arteries, required to accommodate the increased maternal blood flow to the intervillous space of the placenta as pregnancy advances. Much of the vascular endothelium and the underlying medial smooth muscle is replaced by trophoblasts, and fibrin or fibrinoid forms a major morphological feature of the arterial walls. Compared with endothelial cells, the trophoblast lining decidual spiral arteries have a reduced capacity to lyse fibrin, and recent studies have shown this to be caused by high levels of plasminogen activator inhibitors (PAI-1 and PAI-2).
In pregnancies complicated by intrauterine fetal growth retardation (IUGR), with or without superimposed preeclampsia, a restricted physiological adaptation of uteroplacental spiral arteries is coupled with vascular lesions containing increased fibrin deposition. Significantly higher levels of PAI-1 are found in blood from the uterine vein at delivery and in tissue extracts of the placenta in these pregnancies than are found in normal pregnancy.
Recent tissue culture studies have provided new information on the role of trophoblast cells in maintaining hemostatic control in the uteroplacental circulation in pregnancy. Cytotrophoblast cells isolated from the placenta and placental bed from IUGR pregnancies express significantly higher levels of PAI-1, coupled with a significant decrease in plasminogen activator activity, compared with trophoblast cells from normal pregnancy maintained in culture. This localized increased production of PAI-1 may play an important part in restricting endovascular trophoblast invasion in early pregnancy and increasing fibrin deposition and reducing uteroplacental blood flow in pregnancies complicated by IUGR.
Keywords:
Pregnancy - uteroplacental circulation - plasminogen activator inhibitor - PAI-1 - PAI-2 - trophoblasts - intrauterine growth retardation
