Early Origins of Adult Health Research Group, University of South Australia, Adelaide, SA, Australia, 5001.
School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, SA, Australia, 5001.
J Physiol. 2019 Oct;597(20):5063-5077. doi: 10.1113/JP278110. Epub 2019 Oct 1.
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.
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 and as 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.
在妊娠的关键发育期，基质限制会使后代易患心血管疾病。本研究旨在确定在一种可能对慢性胎儿导管插入术进行动物模型中，母体白藜芦醇（RSV）治疗的效果，并且器官成熟的时间反映了人类的情况。母体 RSV 治疗增加了子宫动脉血流量、胎儿氧合和胎儿体重。胎儿循环中未检测到 RSV，表明它可能不会穿过羊胎盘。本研究强调 RSV 作为一种可能的干预措施，以恢复胎盘功能不全的妊娠中的胎儿基质供应。
在妊娠的关键发育期，宫内环境不佳，基质供应减少，使后代易患非传染性疾病，如心血管疾病（CVD）。改善这些妊娠中的胎儿基质供应可能会减轻这些后代对成年后 CVD 的易感性。本研究旨在确定母体白藜芦醇（RSV）补充对子宫动脉血流的影响，以及 RSV 对人妊娠慢性导管化绵羊模型中胎儿心脏的直接影响。母体 RSV 治疗显著增加了相位对比磁共振成像测量的子宫动脉血流量、平均胎心率和胎儿体重。胎儿循环中未检测到 RSV，并且治疗组之间组蛋白/蛋白质去乙酰化酶 SIRT1 的 mRNA 和蛋白表达没有差异。母体 RSV 补充对胎儿左心室 AKT/mTOR 或 CAMKII 信号没有影响。母体 RSV 补充能够增加胎儿的氧合和生长，在一种心脏发育与人类相似的动物模型中。
