Yamada L, Chong S
Epigenetics Group,Translational Research Institute,Mater Research Institute - The University of Queensland,Woolloongabba,QLD,Australia.
J Dev Orig Health Dis. 2017 Feb;8(1):30-43. doi: 10.1017/S2040174416000507. Epub 2016 Sep 9.
The field of Developmental Origins of Health and Disease (DOHaD) seeks to understand the relationships between early-life environmental exposures and long-term health and disease. Until recently, the molecular mechanisms underlying these phenomena were poorly understood; however, epigenetics has been proposed to bridge the gap between the environment and phenotype. Epigenetics involves the study of heritable changes in gene expression, which occur without changes to the underlying DNA sequence. Different types of epigenetic modifications include DNA methylation, post-translational histone modifications and non-coding RNAs. Increasingly, changes to the epigenome have been associated with early-life exposures in both humans and animal models, offering both an explanation for how the environment may programme long-term health, as well as molecular changes that could be developed as biomarkers of exposure and/or future disease. As such, epigenetic studies in DOHaD hold much promise; however, there are a number of factors which should be considered when designing and interpreting such studies. These include the impact of the genome on the epigenome, the tissue-specificity of epigenetic marks, the stability (or lack thereof) of epigenetic changes over time and the importance of associating epigenetic changes with changes in transcription or translation to demonstrate functional consequences. In this review, we discuss each of these key concepts and provide practical strategies to mitigate some common pitfalls with the aim of providing a useful guide for future epigenetic studies in DOHaD.
健康与疾病的发育起源（DOHaD）领域旨在了解生命早期环境暴露与长期健康和疾病之间的关系。直到最近，人们对这些现象背后的分子机制仍知之甚少；然而，表观遗传学被认为可以填补环境与表型之间的空白。表观遗传学涉及对基因表达中可遗传变化的研究，这种变化在不改变基础DNA序列的情况下发生。不同类型的表观遗传修饰包括DNA甲基化、翻译后组蛋白修饰和非编码RNA。越来越多的研究表明，表观基因组的变化与人类和动物模型中的生命早期暴露有关，这既解释了环境如何影响长期健康，也揭示了可能作为暴露和/或未来疾病生物标志物的分子变化。因此，DOHaD领域的表观遗传学研究前景广阔；然而，在设计和解释此类研究时，有许多因素需要考虑。这些因素包括基因组对表观基因组的影响、表观遗传标记的组织特异性、表观遗传变化随时间的稳定性（或缺乏稳定性）以及将表观遗传变化与转录或翻译变化相关联以证明功能后果的重要性。在这篇综述中，我们讨论了这些关键概念，并提供了一些实用策略来避免一些常见的陷阱，旨在为DOHaD未来的表观遗传学研究提供有用的指导。
