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Environ Int. 2018 May;114:77-86. doi: 10.1016/j.envint.2018.02.014. Epub 2018 Feb 27.

Epigenetics as a mechanism linking developmental exposures to long-term toxicity.

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INSERM UMR-S 1124, Université Paris Descartes, Paris, France; Service de Biochimie Métabolomique et Protéomique, Hôpital Necker Enfants Malades, AP-HP, Paris, France. Electronic address:
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, and Centre for Occupational and Environmental Medicine, Stockholm County Council, Sweden.
Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, F-69008 Lyon, France.
Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, 85764 Neuherberg, Germany; Technische Universität München, Experimental Genetics, 85354 Freising, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Epidemiology, Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Hanover, NH, USA.
Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, United States.
NIEHS, Research Triangle Park, NC, USA.
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, 1664 North Virginia Street, Reno, NV 89557, USA MS575; Department of Biology, University of Nevada, Reno, 1664 North Virginia Street, Reno, NV 89557, USA.
INSERM UMR-S973, Molécules Thérapeutiques in silico, University of Paris Diderot, Paris, France.
Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, University Grenoble Alpes, Grenoble, France.
Program in Endocrine Disruption Strategies, Commonweal, Bolinas, CA, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Environmental Medicine, University of Southern Denmark, Odense, Denmark.
Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.


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.


Developmental vulnerability; Endocrine disrupting compounds; Mechanistic toxicology; Particulate matter; Tobacco smoking

[Available on 2019-05-01]

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