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Predicting Later-Life Outcomes of Early-Life Exposures
Boekelheide, K., B. Blumberg, R. E. Chapin, I. L. COTE, H. Graziano, A. Janesick, A. Janesick, R. Lane, K. Lillycrop, L. Myatt, C. States, K. Thayer, M. P. Waalkes, AND J. M. ROGERS. Predicting Later-Life Outcomes of Early-Life Exposures. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 120(10):1353-61, (2012).
This review derives in large part from a National Research Council workshop held in WashingtonJ DCin October 2010 to articulate the current state of understanding of later life diseases resulting from early life exposures mediated through epigenetic mechanisms, to determine the scope of the problem, and to discuss a potential agenda for future research. Exposure of the fetus in utero to an adverse event or stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later life expression of these early life events. Alterations in epigenetic processes can lead to profound changes in phenotype and have been implicated in the pathogenesis of many human diseases. Given that this is a rapidly developing area of scientific Inquiry, this is an appropriate time to assess the state of the science, to develop research recommendations, and to strategize about how to incorporate this new knowledge into health protective practices.
Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from early-life exposures in order to identify in utero and postnatal indicators of later-life diseases, develop an agenda for future research, and consider the risk assessment implications of this emerging knowledge.Methods: This review was developed based on our participation in a National Research Council workshop titled "Use of in Utero and Postnatal Indicators to Predict Health Outcomes Later in Life: State of the Science and Research Recommendations." We used a case study approach to highlight the later-life consequences of early-life malnutrition and arsenic exposure.Discussion: The environmental sensitivity of the epigenome is viewed as an adaptive mechanism by which the developing organism adjusts its metabolic and homeostatic systems to suit the anticipated extrauterine environment. Inappropriate adaptation may produce a mismatch resulting in subsequent increased susceptibility to disease. A nutritional mismatch between the prenatal and postnatal environments, or early-life obesogen exposure, may explain at least some of the recent rapid increases in the rates of obesity, type 2 diabetes, and cardiovascular diseases. Early-life arsenic exposure is also associated with later-life diseases, including cardiovascular disease and cancer.Conclusions: With mounting evidence connecting early-life exposures and later-life disease, new strategies are needed to incorporate this emerging knowledge into health protective practices.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION