Giussani Dino A, Niu Youguo, Herrera Emilio A, Richter Hans G, Camm Emily J, Thakor Avnesh S, Kane Andrew D, Hansell Jeremy A, Brain Kirsty L, Skeffington Katie L, Itani Nozomi, Wooding F B Peter, Cross Christine M, Allison Beth J
Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK,
Adv Exp Med Biol. 2014;814:77-87. doi: 10.1007/978-1-4939-1031-1_7.
The quality of the intrauterine environment interacts with our genetic makeup to shape the risk of developing disease in later life. Fetal chronic hypoxia is a common complication of pregnancy. This chapter reviews how fetal chronic hypoxia programmes cardiac and endothelial dysfunction in the offspring in adult life and discusses the mechanisms via which this may occur. Using an integrative approach in large and small animal models at the in vivo, isolated organ, cellular and molecular levels, our programmes of work have raised the hypothesis that oxidative stress in the fetal heart and vasculature underlies the mechanism via which prenatal hypoxia programmes cardiovascular dysfunction in later life. Developmental hypoxia independent of changes in maternal nutrition promotes fetal growth restriction and induces changes in the cardiovascular, metabolic and endocrine systems of the adult offspring, which are normally associated with disease states during ageing. Treatment with antioxidants of animal pregnancies complicated with reduced oxygen delivery to the fetus prevents the alterations in fetal growth, and the cardiovascular, metabolic and endocrine dysfunction in the fetal and adult offspring. The work reviewed offers both insight into mechanisms and possible therapeutic targets for clinical intervention against the early origin of cardiometabolic disease in pregnancy complicated by fetal chronic hypoxia.
子宫内环境的质量与我们的基因构成相互作用，从而塑造日后患疾病的风险。胎儿慢性缺氧是一种常见的妊娠并发症。本章回顾了胎儿慢性缺氧如何在成年后代中引发心脏和内皮功能障碍，并讨论了其可能的发生机制。通过在体内、离体器官、细胞和分子水平上对大型和小型动物模型采用综合方法，我们的研究项目提出了这样一个假说：胎儿心脏和血管中的氧化应激是产前缺氧导致成年后心血管功能障碍的潜在机制。与母体营养变化无关的发育性缺氧会促进胎儿生长受限，并引发成年后代心血管、代谢和内分泌系统的变化，而这些变化通常与衰老过程中的疾病状态相关。对伴有胎儿氧输送减少的动物妊娠使用抗氧化剂进行治疗，可预防胎儿生长改变以及胎儿和成年后代的心血管、代谢和内分泌功能障碍。所综述的这项研究工作，既深入探讨了相关机制，也为临床干预因胎儿慢性缺氧而并发的妊娠中心血管代谢疾病的早期起源提供了可能的治疗靶点。
