Extensive human epidemiologic and animal model data indicate that during critical periods of prenatal and postnatal mammalian development, nutrition and other environmental stimuli influence developmental pathways and thereby induce permanent changes in metabolism and chronic disease susceptibility. The biologic mechanisms underlying this "developmental origins hypothesis" are poorly understood. This review focuses on the likely involvement of epigenetic mechanisms in the developmental origins of health and disease (DOHaD). We describe permanent effects of transient environmental influences on the developmental establishment of epigenetic gene regulation and evidence linking epigenetic dysregulation with human disease. We propose a definition of "epigenetic epidemiology" and delineate how this emerging field provides a basis from which to explore the role of epigenetic mechanisms in DOHaD. We suggest strategies for future human epidemiologic studies to identify causal associations between early exposures, long-term changes in epigenetic regulation, and disease, which may ultimately enable specific early-life interventions to improve human health.

中文翻译：

---

发育起源假说的表观遗传流行病学。

大量的人类流行病学和动物模型数据表明，在产前和产后哺乳动物发育的关键时期，营养和其他环境刺激会影响发育途径，从而引起新陈代谢的永久性变化和慢性疾病的易感性。这种“发育起源假说”的生物学机制知之甚少。这项审查侧重于表观遗传机制可能参与健康和疾病的发展起源（DOHaD）。我们描述了短暂的环境影响对表观遗传基因调控的发展建立的永久性影响，以及将表观遗传失调与人类疾病联系起来的证据。我们提出“表观流行病学”的定义 并描述这一新兴领域如何为探索表观遗传机制在DOHaD中的作用提供基础。我们建议用于未来人类流行病学研究的策略，以识别早期暴露，表观遗传调控的长期变化与疾病之间的因果关系，这最终可能使特定的早期生命干预措施能够改善人类健康。