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Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives

Philippe Grandjean Robert Barouki 1 David C. Bellinger Ludwine Casteleyn Lisa H. Chadwick Sylvaine Cordier 2 Ruth A. Etzel Kimberly A. Gray Eun-Hee Ha Claudine Junien 3 Margaret Karagas Toshihiro Kawamoto B. Paige Lawrence Frederica P. Perera Gail S. Prins Alvaro Puga Cheryl S. Rosenfeld David H. Sherr Peter D. Sly William Suk Qi Sun 4 Jorma Toppari 5 Peter Hazel Cheryl L. Walker Jerrold J Heindel
1 U747 - Pharmacologie, toxicologie et signalisation cellulaire
2 Irset - Institut de recherche en santé, environnement et travail
3 BDR - Biologie du Développement et Reproduction
4 Life Sciences Core Laboratories Center
5 Institute of Biomedicine/Physiology
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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Philippe Grandjean, Robert Barouki, David C. Bellinger, Ludwine Casteleyn, Lisa H. Chadwick, et al.. Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives. Endocrinology, Endocrine Society, 2015, 2016 (1), pp.10-16. ⟨10.1210/EN.2015-1350⟩. ⟨hal-01187409⟩

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