Uteroplacental hemostasis in intrauterine fetal growth retardation

During pregnancy, extensive hemostatic changes occur in the uteroplacental circulation. Invading endovascular trophoblast cells induce physiological a daptations of uterine spiral arteries, required to accommodate the increase d maternal blood flow to the intervillous space of the placenta as pregnanc y advances. Much of the vascular endothelium and the underlying medial smoo th muscle is replaced by trophoblasts, and fibrin or fibrinoid forms a majo r morphological feature of the arterial walls. Compared with endothelial ce lls, the trophoblast lining decidual spiral arteries have a reduced capacit y to lyse fibrin, and recent studies have shown this to be caused by high l evels of plasminogen activator inhibitors (PAI-I and PAI-2). In pregnancies complicated by intrauterine fetal growth retardation (IUGR), with or without superimposed preeclampsia, a restricted physiological adap tation of uteroplacental spiral arteries is coupled with vascular lesions c ontaining increased fibrin deposition. Significantly higher levels of PAI-1 are found in blood from the uterine vein at delivery and in tissue extract s 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 c irculation in pregnancy. Cytotrophoblast cells isolated from the placenta a nd placental bed from IUGR pregnancies express significantly higher levels of PAI-I, coupled with a significant decrease in plasminogen activator acti vity, compared with trophoblast cells from normal pregnancy maintained in c ulture. This localized increased production of PAI-1 may play an important part in restricting endovascular trophoblast invasion in early pregnancy an d increasing fibrin deposition and reducing uteroplacental blood flow in pr egnancies complicated by IUGR.