Placental angiogenesis and immune-privilege in normal and pathological pregnancies

Abstract

Proper placentation is a prerequisite for normal fetal development and investigations were conducted on expression and secretion profiles of GFs and CAMs. Studies on the pivotal angiogenic factors, angiogenin as well as PlGF, EGF and VEGF were conducted in normal and in pregnancies complicated by PE and IUGR. Angiogenin was identified for the first time to be produced in a gestation dependent manner with significantly increased levels of expression and secretion in PE and IUGR. On the other hand, levels of VCAM-1 and its mRNA were decreased in a gestation dependent manner, but these levels were further decreased in IUGR placentae, suggesting that diminished levels were associated with placental insufficiency. Moreover, experiments using hypoxia provided evidence for significantly enhanced expression and secretion of angiogenin with a concomitant loss of VCAM-1, thus indicating a role for these pivotal peptides in IUGR. Additional studies pertaining to immune-privilege of trophoblasts and choriocarcinoma have also been provided which indicated co-expression of Fas and FasL in malignant trophoblasts. The data suggest that choriocarcinoma cells could evade immune attack by down regulation of Fas receptors and by killing lymphocytes through expression of FasL.