Functional and molecular analysis of umbilical vessels endothelial cells of fetuses with normal growth and intrauterine growth restriction.

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

March 4-7, FIRENZE, ITALY.

Congreso; 14th World Congress of Gynecological Endocrinology, II Congresso ISGE Italia; 2010

INTERNATIONAL SOCIETY OF GYNECOLOGICAL ENDOCRINOLOGY (ISGE)

Increasing evidence indicates that a dysfunction of feto-placental endothelial cells plays a prominent role in intrauterine growth restriction (IUGR). We investigated the role of the umbilical vessels endothelial cells in pregnancies affected by IUGR, by combining the results of Doppler with the molecular analysis of umbilical vein endothelial cells (HUVECs) and the nitric oxide (NO), asymmetric dimethylarginine (ADMA) and S-nitrosohemoglobin (S-NOHb) umbilical levels, and by determining the molecular phenotype of umbilical HUVEC with a gene array strategy. The IUGR is associated with an increase of NO release by HUVECs. No difference in umbilical vein ADMA concentration were observed between foetuses affected by IUGR 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 in case of severe asymmetric growth. The fetal hemodynamic alterations found in IUGR by Doppler velocimetry are associated with greater NO increase. Finally, the IUGR is related with a specific gene expression phenotype of HUVECs. We hypothesize that the hypoxic stimulus of IUGR increases umbilical vessels NO levels as a compensatory response, overall in the venous district and in presence of greater feto-placental flow alterations. It seems that the S-NOHb under fetal hypoxic conditions is a source of [NO_] equivalents for the umbilical vessels wall. Moreover, endogenous NO-synthase inhibitors may play a role in the arterial compensatory response to feto-placental ischemia. This trial suggests that the NO system plays an important role in IUGR.