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Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives
Philippe Grandjean1, Robert Barouki1, David C Bellinger1
1Departments of Environmental Health (P.G., D.C.B.) and Nutrition (Q.S.), Harvard T.H. Chan School of Public Health; Children's Hospital (D.C.B.), Harvard Medical School; and Channing Division of Network Medicine (Q.S.), Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115; Department of Environmental Medicine (P.G.), Institute of Public Health, University of Southern Denmark, 5000 Odense, Denmark; Institut National de la Santé et de la Recherche Médicale unit 1124 (R.B.), Université Paris Descartes, Hôpital Necker enfants malades, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France; University of Leuven (L.C.), Center for Human Genetics, 3000 Leuven, Belgium; Division of Extramural Research and Training (L.H.C., K.A.G., W.S., J.J.H.), National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709; Institut National de la Santé et de la Recherche Médicale, Unit 1085 (S.C.), University Rennes I, F-35000 Rennes, France; Joseph J. Zilber School of Public Health (R.A.E.), University of Wisconsin, Milwaukee, Wisconsin 53201; Department of Preventive Medicine (E.-H.H.), School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea; Institut National de la Recherche Agronomique (C.J.), MR Unité Mixte de Recherche 1198 Biologie du Développement et Reproduction, F-78350 Jouy-en-Josas, France; Université Versailles-St-Quentin (C.J.), 78000 Versailles, France; Children's Environmental Health and Disease Prevention Research Center and Department of Epidemiology, Geisel School of Medicine at Dartmouth (M.K.), Hanover, New Hampshire 03766; Department of Environmental Health (T.K.), University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Environmental Medicine (B.P.L.), University of Rochester School of Medicine and Dentistry, Rochester, New York 14642; Department of Environmental Health Sciences and Columbia Center for Children's Environmental Heal
Abstract:
The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.
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