Role of endothelial cells nitric oxide system in intrauterine restricted growth.

S. PISANESCHI; A.M. SANCHEZ; S. BEGLIUOMINI; F.A.L. STRIGINI; P. GHIRRI; A. BOLDRINI; A.R. GENAZZANI; F. COCEANI; T. SIMONCINI

10-13 September, Rome, Italy

Congreso; 8th ESG Congress of the European Society of Gynecology.; 2009

European Society of Gynecology

Increasing evidence indicates that a dysfunction of feto-placental endothelial cells plays a prominent role in IUGR. We investigated the role of the NO system in pregnancies affected by IUGR, by combining the analysis of NO, ADMA and S-NOHb in umbilical vessels in normal and IUGR pregnancies and by determining the molecular phenotype of umbilical HUVEC with a gene array strategy. IUGR is associated with increased NO umbilical levels and decreased ADMA umbilical artery levels. No difference in umbilical vein ADMA concentration were observed between IUGR foetuses and controls. High S-NOHb levels were noted in umbilical vessel of pregnancy complicated by IUGR. The umbilical NO increase mostly occurs in blood flow toward the fetus and it is not any longer satisfactory when the ponderal index (PInd) decreases. Fetal hemodynamic alterations found in IUGR by Doppler velocimetry are associated with greater NO increases. IUGR is related with a specific gene expression phenotype of HUVECs. We hypothesize that hypoxia increases IUGR umbilical vessels NO levels, until a deterioration of fetal conditions occurs. Interestingly, the compensatory response to feto-placental ischemia is higher in presence of greater feto-placental flow alterations. SNOHb under fetal hypoxic conditions may be a source of [NO_] equivalents for the umbilical vessels wall. Moreover, endogenous NO-synthase inhibitors may play a role in the compensatory response in umbilical artery to feto-placental ischemia. This trial suggests that endothelial cells and the NO system play a major role in IUGR.