Combined functional and molecular analysis of endothelial cells from umbilical vessels of fetuses with normal or restricted intrauterine growth.

S. PISANESCHI; A.M. SANCHEZ; S. GARIBALDI; L. GOGLIA; V. TOSI; S. BEGLIUOMINI; A.R. GENAZZANI; F. COCEANI; T. SIMONCINI

March 5-8, Venezia, Italy

Congreso; 13th World Congress on Human Reproduction.; 2009

There is abundant evidence that the endothelium regulates the maintenance of vascular tone and structure. We evaluated the functional role of the umbilical vessels endothelial cells in the pathophysiology of restricted intrauterine growth, combining the data from Doppler velocimetry with HUVEC molecular analysis and of umbilical and neonatal blood Snitrosohemoglobin, nitric oxide and asymmetric dimethylarginine. We analyzed newborns 25th centile. The restricted growth is related with an increased HUVEC nitric oxide release, a higher nitric oxide umbilical levels, and decreased asymmetric dimethylarginine umbilical artery levels. No difference in umbilical vein ADMA concentration were observed between foetuses restricted for growth and controls. High umbilical s-nitrosohemoglobin levels were noted in pregnancy with restricted growth. NO increase mostly occur in umbilical vein, but it is not any longer satisfactory when the ponderal index dramatically falls down. Fetal hemodynamic alterations found by Doppler velocimetry are associated with greatest NO increase. We hypothesize that hypoxic stimulus of restricted growth increases umbilical NO levels, until a great deterioration of fetal condition. The major compensatory response to feto-placental ischemia occurs in blood flow toward the fetus and it is higher in presence of great feto-placental flow alteration. S-NOHb under fetal hypoxic conditions may be a source of [NO_] equivalents for the umbilical vessel wall. In addition, we propose the role of circulating endogenous NO-synthase inhibitors in the compensatory response to feto-placental ischemia in umbilical artery. The restricted intrauterine growth is associated with a specific gene expression phenotype of umbilical vein endothelial cells.