Role of the nitric oxide system related to fetal growth in the advanced age women.

PISANESCHI S,; SANCHEZ AM, ; STRIGINI FAL,; GHIRRI P,; BOLDRINI A, ; GENAZZANI AR; COCEANI F,; SIMONCINI T.

Roma

Congreso; 13th World Congress on Menopause.; 2011

Feto-placental vascular dysfunction is a key feature of fetal growth restriction (FGR). We measured nitrite formation (NO2), asymmetric dimethylarginine (ADMA) and nitrosohemoglobin (NOHb) in the feto-placental circulation of pregnancies with fetal growth restriction and in the peripheral blood of newborns in advanced age women. Blood measurements were related with Doppler examination of the feto-placental circulation and with a gene-array analysis of umbilical endothelial cells. We enrolled 60 term pregnancies in over 35 years women with normal or small-for-gestational-age (SGA) newborns, 15 preterm pregnancies with SGA infants and 12 twin pregnancies with discordant growth of the fetuses. We found increased NO2 and NOHb in the feto-placental circulation of SGA pregnancies. Conversely, ADMA levels were lower in umbilical artery blood. Umbilical vein endothelial cells (HUVEC) from the same SGA pregnancies presented a more active endothelial nitric oxide synthase (eNOS) with a greater yield of NO2. Increased fetoplacental NO2 and decreased NOHb coincided with Doppler alterations. Mini-array analysis of HUVEC evidenced up-regulation of vasodilatory transcripts, such as eNOS, along with down-regulation of transcripts for vasoconstricting mechanisms and angiogenesis. SGA newborns manifested a post-natal rise of circulating NO2 and NOHb. Concluding, pregnancies with a SGA fetus present an activation of the NO system with a functional modification of both feto-placental endothelial cells and the fetus. Pre-natal Doppler velocimetric variables are changed concomitantly. This set of responses may reflect an adaptive process to maintain feto-placental blood, but its persistence after birth may represent an abnormal programming with potential adverse consequences.