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.

各种实验和流行病学研究为健康与疾病的发展起源 (DOHaD) 概念提供了支持。然而，说明生命早期暴露的中长期影响的实际机制仍不清楚。表观遗传改变，例如 DNA 甲基化、组蛋白修饰和某些 RNA 的表达的变化，已被认为是环境压力源长期健康影响的可能介质。

本报告记录了上次在日本举行的产前规划和毒性会议期间的讨论和结论。它的第一个目标是提出许多标准，这些标准对于支持表观遗传学在 DOHaD 中的主要贡献和环境压力效应的代际传递至关重要。主要标准是压力源的完整特征、实际暴露窗口、目标组织和功能、表观遗传变化的特异性以及这些变化与健康结果之间联系的生物学合理性。第二个目的是讨论许多压力因素的长期影响，如吸烟、空气污染和内分泌干扰物，以确定支持表观遗传机制参与的论点。根据制定的标准，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表观遗传机制参与环境暴露的代际和跨代影响的证据，并特别讨论胎盘和精子的作用。

虽然这篇文章不是系统综述，也不是详尽无遗，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贡献，并为未来的研究提供了见解。