Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

• DOI: 10.1371/journal.pone.0045294
• Publication Date: 2012-09-30T06:27:02Z
• Authors: Silvia Pisaneschi; Francesca A. L. S...; Angel M. Sanchez; Silvia Begliuomini; Elena Casarosa; Andrea Ripoli; Paolo Ghirri; Antonio Boldrini; Bruno Fink; Andrea R. Genazzani; Flavio Coceani; Tommaso Simoncini
• Keywords: Adult; Nitric Oxide Synthase Type III; Endothelial cells; Science; Placenta; Arginine; Nitric Oxide; Hemoglobins; 03 medical and health sciences; Fetus; Pregnancy; https://purl.org/becyt/ford/3.2; Humans; https://purl.org/becyt/ford/3; Nitrites; nitric oxide system; 0303 health sciences; Fetal Growth Retardation; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Q; R; Infant, Newborn; Endothelial Cells; Infant, Low Birth Weight; Fetal Blood; Adaptation, Physiological; S- nitrosohemoglobin; 3. Good health; Medicine; Female; Endothelium, Vascular; Fetal Growth Restriction; Research Article

Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system.Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12).Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring.Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life.