INSERM UMR-S 1124, Université Paris Descartes, Paris, France; Service de Biochimie Métabolomique et Protéomique, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, and Centre for Occupational and Environmental Medicine, Stockholm County Council, Sweden.
Environ Int. 2018 May;114:77-86. doi: 10.1016/j.envint.2018.02.014. Epub 2018 Feb 27.
A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylation, histone modifications and the expression of certain RNAs have been suggested as possible mediators of long-term health effects of environmental stressors. This report captures discussions and conclusions debated during the last Prenatal Programming and Toxicity meeting held in Japan. Its first aim is to propose a number of criteria that are critical to support the primary contribution of epigenetics in DOHaD and intergenerational transmission of environmental stressors effects. The main criteria are the full characterization of the stressors, the actual window of exposure, the target tissue and function, the specificity of the epigenetic changes and the biological plausibility of the linkage between those changes and health outcomes. The second aim is to discuss long-term effects of a number of stressors such as smoking, air pollution and endocrine disruptors in order to identify the arguments supporting the involvement of an epigenetic mechanism. Based on the developed criteria, missing evidence and suggestions for future research will be identified. The third aim is to critically analyze the evidence supporting the involvement of epigenetic mechanisms in intergenerational and transgenerational effects of environmental exposure and to particularly discuss the role of placenta and sperm. While the article is not a systematic review and is not meant to be exhaustive, it critically assesses the contribution of epigenetics in the long-term effects of environmental exposures as well as provides insight for future research.
多种实验和流行病学研究支持健康与疾病的发育起源（DOHaD）概念。然而，导致早期生活暴露产生中、长期影响的实际机制仍不清楚。DNA 甲基化、组蛋白修饰和特定 RNA 的表达等表观遗传改变被认为是环境应激源对长期健康影响的可能介导物。本报告记录了在日本举行的最后一次产前编程和毒性会议上的讨论和结论。其首要目的是提出一些标准，这些标准对于支持 DOHaD 中表观遗传学的主要贡献以及环境应激源效应的代际传递至关重要。主要标准是应激源的全面特征、实际暴露窗口、靶组织和功能、表观遗传变化的特异性以及这些变化与健康结果之间的联系的生物学合理性。第二个目的是讨论吸烟、空气污染和内分泌干扰物等多种应激源的长期影响，以确定支持涉及表观遗传机制的论据。基于制定的标准，将确定缺失的证据和对未来研究的建议。第三个目的是批判性地分析支持环境暴露的代际和跨代效应中涉及表观遗传机制的证据，并特别讨论胎盘和精子的作用。虽然本文不是系统评价，也不打算面面俱到，但它批判性地评估了表观遗传学在环境暴露的长期影响中的作用，并为未来的研究提供了思路。
