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Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth
Author(s) -
Darby Jack R. T.,
Saini Brahmdeep S.,
Soo Jia Yin,
Lock Mitchell C.,
Holman Stacey L.,
Bradshaw Emma L.,
McInnes Steven J. P.,
Voelcker Nicolas H.,
Macgowan Christopher K.,
Seed Mike,
Wiese Michael D.,
Morrison Janna L.
Publication year - 2019
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp278110
Subject(s) - fetus , offspring , medicine , fetal circulation , gestation , endocrinology , in utero , pregnancy , conceptus , intrauterine growth restriction , resveratrol , placenta , physiology , biology , pharmacology , genetics
Key points Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency.Abstract Suboptimal in utero environments with 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‐onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal P a O 2and S a O 2as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.