Impact of resveratrol mediated increased uterine artery blood flow on fetal haemodynamics, blood pressure, and oxygenation in sheep.

NEW FINDINGS Uterine artery blood flow helps maintain fetal oxygen and nutrient delivery  This study investigates the effects of increased uterine artery blood flow mediated by resveratrol on fetal growth, haemodynamics, blood pressure regulation, and oxygenation in a sheep model of pregnancy Fetuses from resveratrol treated ewes were significantly larger and exhibited a haemodynamic profile that may promote peripheral growth Absolute uterine artery blood flow positively correlated with umbilical vein oxygen saturation, absolute fetal oxygen delivery, and fetal growth Increasing uterine artery blood flow with compounds like resveratrol may have clinical significance for pregnancy conditions where fetal growth and oxygenation are compromised ABSTRACT: High placental vascular resistance hinders uterine artery (UtA) blood flow and fetal substrate delivery. In the same group of animals as the present study, we have previously shown that resveratrol (RSV) increases UtA blood flow, fetal weight, and oxygenation in a sheep model of human pregnancy. However, the mechanisms behind changes in growth and the effects of increases in UtA blood flow on fetal circulatory physiology have yet to be investigated. Twin bearing ewes received subcutaneous vehicle (VEH, n = 5) or RSV (n = 6) delivery systems at 113 days (d) gestation (term = 150d). MRI was performed at 123-124d to quantify fetal volume, blood flow, and oxygen saturation (SO2 ) of major fetal vessels. At 128d, intravenous infusions of sodium nitroprusside (SNP) and phenylephrine (PE) were administered to study the vascular tone of the fetal descending aorta. Maternal RSV increased fetal body volume (P = 0.0075) and weight (P = 0.0358) with no change in brain volume or brain weight. There was a positive relationship between absolute UtA blood flow and umbilical vein (UV) SO2 , absolute fetal oxygen delivery (DO2 ), and combined fetal twin volume (all P≤0.05). There were no differences between groups in fetal haemodynamics or blood pressure regulation except for higher blood flow to the lower body in RSV fetuses (P = 0.0170). The observed increase in fetal weight may be helpful in pregnancy conditions where fetal growth and oxygen delivery are compromised. Further preclinical investigations on the mechanism(s) accounting for these changes and the potential to improve growth in complicated pregnancies are warranted. This article is protected by copyright. All rights reserved.