Over-expression and secretion of angiogenin in intrauterine growth retardation placenta

Abstract

Human angiogenin is a potent inducer of neovascularization. There is a strong evidence to suggest that it might be involved in morphological and angiogenic changes in the placenta, that are necessary for a successful fetal outcome during pregnancy. However, its precise role in the pathogenesis of abnormal pregnancies is yet unknown. Intrauterine growth retardation (IUGR), an abnormal pregnancy is not a specific disease entity per se, but rather a manifestation of many possible fetal and maternal disorders. In this study, we demonstrated, for the first time, that placental explants in vitro secrete significantly elevated levels of angiogenin in placental tissues from patients with IUGR. We also observed enhanced mRNA expression in placenta from these patients. In addition, using the immunohistochemical methods, we observed identical staining of angiogenin to villous syncytiotrophobalst and fetal endothelial cells in both IUGR and normal placenta. Functionally active placental explants were used to detect immunoreactive angiogenin in conditioned media of all the samples from IUGR placenta and normal term group. The mean levels of angiogenin secreted by IUGR placenta were 1.4-, 1.6-, and 1.3-fold higher (P < 0.01) than normal term samples at 24, 48, and 72 hr of culture, respectively. Expression profiles of angiogenin from term and IUGR cases are in agreement with its mRNA levels and immunoblot analysis. In conclusion, the significant elevated levels of angiogenin in IUGR placenta may provide a molecular mechanism for the abnormal placental development. © 2003 Wiley-Liss, Inc.