Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Subcutaneous sustained release maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe (#13)

Jack R.T. Darby 1 , Brahmdeep S Saini 2 , Jia Yin Soo 1 , Mitchell C Lock 1 , Stacey L Holman 1 , Emma L Bradshaw 1 , Steven J.P. McInnes 1 , Nicolas H Voelcker 3 , Christopher K Macgowan 2 , Mike Seed 2 , Michael D Wiese 1 , Janna L Morrison 1
  1. University of South Australia, Adelaide, Australia
  2. University of Toronto and The Hospital for Sick Children, Toronto, Canada
  3. Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia

Reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult CVD. This study aimed to determine the effect of maternal Resveratrol (RSV) supplementation on uterine artery blood flow as well as the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. At 113 days (d) gestation (GA; term, 150d), Merino ewes carrying twin fetuses were randomly assigned to either a vehicle (n=9) or RSV (n=6) treatment group. Polycaprolactone drug delivery discs containing either vehicle or RSV were implanted subcutaneously on the back of the ewes’ neck. At 119-120d GA vascular catheters into the fetal femoral artery, vein and amniotic cavity. At 123-4d GA, phase-contrast MRI was used to measure uterine artery blood flow. Maternal and fetal blood samples were collected across gestation until post mortem at 130d GA for determination of plasma resveratrol concentrations by LC-MS. mRNA and protein expression of signalling molecules known to be responsive to resveratrol were determined by qRT-PCR and Western Blot. Maternal RSV treatment significantly increased uterine artery blood flow (Figure 1), mean gestational fetal PaO2, and SaO2 as well as fetal weight (Figure 1). RSV was not detectable in the fetal circulation and mRNA and protein expression of the RSV responsive histone/protein deacetylase SIRT1 remained unchanged between treatment groups Therefore maternal RSV supplementation is capable of increasing fetal oxygenation and weight through increased uterine artery blood flow in an animal model that parallels human cardiac development. However, RSV may not cross the sheep placenta; providing a novel animal model for teasing apart the direct effects of resveratrol on the fetus from the beneficial effects of RSV acting on the mother. 

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