Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, Zürich, Switzerland; Institute for Neuroscience, Department of Health Science and Technology of the Swiss Federal Institute of Technology (ETH), Zürich, Switzerland; BRAINCITY EMBL-Nencki Center of Excellence for Neural Plasticity and Brain Disorders, Nencki Institute of Experimental Biology, Warsaw, Poland; Department of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Medical Faculty of the University of Zurich, Zurich, Switzerland.
Trends Genet. 2021 Apr;37(4):373-388. doi: 10.1016/j.tig.2020.10.006. Epub 2020 Nov 11.
The possibility that parental life experiences and environmental exposures influence mental and physical health across generations is an important concept in biology and medicine. Evidence from animal models has established the existence of a non-genetic mode of inheritance. This form of heredity involves transmission of the effects of parental exposure to the offspring through epigenetic changes in the germline. Studying the mechanisms of epigenetic inheritance in humans is challenging because it is difficult to obtain multigeneration cohorts, to collect reproductive cells in exposed parents, and to exclude psychosocial and cultural confounders. Nonetheless, epidemiological studies in humans exposed to famine, stress/trauma, or toxicants have provided evidence that parental exposure can impact the health of descendants, in some cases, across several generations. A few studies have also started to reveal epigenetic changes in the periphery and sperm after certain exposures. This article reviews these studies and evaluates the current evidence for the potential contribution of epigenetic factors to heredity in humans. The challenges and limitations of this fundamental biological process, its implications, and its societal relevance are also discussed.
父母的生活经历和环境暴露影响代际间精神和身体健康的可能性,是生物学和医学中的一个重要概念。动物模型的证据已经确立了一种非遗传的遗传模式的存在。这种遗传形式涉及通过生殖系中的表观遗传变化将父母暴露的影响传递给后代。研究人类的表观遗传遗传机制具有挑战性,因为很难获得多代队列,收集暴露父母的生殖细胞,并排除心理社会和文化混杂因素。尽管如此,人类暴露于饥荒、压力/创伤或毒物的流行病学研究已经提供了证据,表明父母的暴露可以影响后代的健康,在某些情况下,甚至可以跨越几代。一些研究也开始揭示某些暴露后外周血和精子中的表观遗传变化。本文综述了这些研究,并评估了表观遗传因素对人类遗传潜在贡献的现有证据。还讨论了这一基本生物学过程的挑战和局限性、其意义及其与社会的相关性。