Shah Amin, Reyes Laura M, Morton Jude S, Fung David, Schneider Jillian, Davidge Sandra T
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
J Physiol. 2016 Mar 1;594(5):1465-82. doi: 10.1113/JP271133. Epub 2015 Nov 4.
Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.
产前缺氧是妊娠并发症的常见后果，会使后代在以后的生活中易患代谢和心血管疾病。我们之前观察到，白藜芦醇可改善成年雄性大鼠后代在产前缺氧和产后高脂（HF）饮食条件下的心血管和代谢健康；然而，白藜芦醇对雌性大鼠后代的影响尚不清楚。我们的目的是确定白藜芦醇可能预防产前缺氧和产后HF饮食的雄性和雌性大鼠后代代谢和心脏功能障碍的机制。在子宫内经历过常氧或缺氧的后代在断奶后喂食HF饮食或添加白藜芦醇的HF饮食9周。在12周龄时评估身体组成、代谢功能、体内心脏功能和离体心脏对缺血再灌注（I/R）损伤的易感性。产前缺氧损害了喂食HF饮食的雄性大鼠后代的代谢功能，但对雌性大鼠后代没有影响，补充白藜芦醇可改善这种情况。产前缺氧还导致喂食HF饮食的雄性大鼠后代心脏I/R损伤后的恢复减少，雌性大鼠后代的恢复减少程度较小。暴露于产前缺氧的雄性和雌性大鼠后代I/R后的心脏氧化应激指标均增强。白藜芦醇改善了I/R损伤后的心脏恢复，并降低了雄性和雌性大鼠后代的超氧化物水平。总之，产前缺氧以性别特异性方式损害代谢和心脏功能。补充白藜芦醇可能改善暴露于产前缺氧的成年雄性和雌性大鼠后代的代谢和心血管健康。
