Perinatology Research Laboratory, Department of Obstetrics and Gynaecology, Medical Research Centre, School of Medicine, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile.
Curr Vasc Pharmacol. 2009 Oct;7(4):513-20. doi: 10.2174/157016109789043883.
The hypothesis of 'Developmental Origins of Health and Disease' (DOHaD) relies on the presence of mechanisms sensing and signalling a diversity of stimuli during fetal development. The mechanisms that have been broadly suggested to be involved in these processes are the epigenetic modifications that could 'record' perinatal stimuli. Since the definition of epigenetic and the associated mechanisms are conflictive, in this review epigenetic was defined as 'chromosome-based mechanisms that can change the phenotypic plasticity in a cell or organism'. The most understood epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications (PTM), ATP-dependent chromatin modifications and non-coding RNAs) and reported evidence for their role in fetal programming were briefly reviewed. The development of the vascular system is strongly influenced by epigenetic mechanisms. For that reason vascular cells are good candidates to be explored regarding epigenetic programming since its proved susceptibility to be imprinted. This has been described in pregnancy diseases such as intra-uterine growth restriction, gestational diabetes and pre-eclampsia, where changes in vascular function are preserved in vitro.
“健康与疾病的发育起源”假说(DOHaD)依赖于在胎儿发育过程中存在感知和传递各种刺激的机制。被广泛认为参与这些过程的机制是表观遗传修饰,它可以“记录”围产期刺激。由于表观遗传和相关机制的定义存在冲突,在本综述中,将表观遗传定义为“基于染色体的机制,可以改变细胞或生物体的表型可塑性”。简要回顾了最被理解的表观遗传机制(即 DNA 甲基化、组蛋白翻译后修饰(PTM)、ATP 依赖性染色质修饰和非编码 RNA)及其在胎儿编程中的作用的报告证据。血管系统的发育强烈受到表观遗传机制的影响。出于这个原因,血管细胞是探索表观遗传编程的良好候选者,因为其被证明易受印迹影响。这在妊娠疾病中如宫内生长受限、妊娠期糖尿病和子痫前期中已经得到描述,其中血管功能的变化在体外得以保留。