Fowden Abigail L, Forhead Alison J
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Exp Physiol. 2009 Jun;94(6):607-25. doi: 10.1113/expphysiol.2008.046359. Epub 2009 Feb 27.
In mammals, including man, epidemiological and experimental studies have shown that a range of environmental factors acting during critical periods of early development can alter adult phenotype. Hormones have an important role in these epigenetic modifications and can signal the type, severity and duration of the environmental cue to the developing feto-placental tissues. They affect development of these tissues both directly and indirectly by changes in placental phenotype. They act to alter gene expression, hence the protein abundance in a wide range of different tissues, which has functional consequences for many physiological systems both before and after birth. By producing an epigenome specific to the prevailing condition in utero, hormones act as epigenetic signals in developmental programming, with important implications for adult health and disease. This review examines the role of hormones as epigenetic signals by considering their responses to environmental cues, their effects on phenotypical development and the molecular mechanisms by which they programme feto-placental development, with particular emphasis on the glucocorticoids.
在包括人类在内的哺乳动物中，流行病学和实验研究表明，在早期发育的关键时期起作用的一系列环境因素能够改变成年后的表型。激素在这些表观遗传修饰中发挥着重要作用，并且能够向发育中的胎儿-胎盘组织传递环境信号的类型、严重程度和持续时间。它们通过胎盘表型的变化直接或间接地影响这些组织的发育。它们作用于改变基因表达，从而改变广泛不同组织中的蛋白质丰度，这对出生前后的许多生理系统都有功能上的影响。通过产生特定于子宫内现有状况的表观基因组，激素在发育编程中充当表观遗传信号，对成年后的健康和疾病具有重要影响。本综述通过考虑激素对环境信号的反应、它们对表型发育的影响以及它们编程胎儿-胎盘发育的分子机制，来探讨激素作为表观遗传信号的作用，尤其着重于糖皮质激素。
