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SOT CCT Conference PPTOX II: Role of Environmental Stressors in the Developmental Origins of Disease—a Huge Success
An international conference on “Prenatal Programming and Toxicology II (PPTOX II): Role of Environmental Stressors in the Developmental Origins of Disease” was held December 7–10, 2009, through the SOT Contemporary Concepts in Toxicology (CCT) Program. This conference followed up PPTOX I that was held in Torshavn, Faroe Islands, in 2007. Over 240 scientists, including more than 75 students and postdocs, from around the world gathered in Miami South Beach to present both animal and human data supporting the hypothesis that environmental exposures during development lead to altered programming that results in increased susceptibility to disease/dysfunction later in life.
The meeting started with overviews of the developmental origins of disease hypothesis focusing on altered nutrition and exposures to environmental chemicals in human and animal models followed by an examination of this hypothesis in the ecological developmental biology field. Overviews of animal models and epigenetics as the underlying mechanism of the altered programming concluded the first night activities. The hypothesis was then examined in more detail in sessions that focused on both the human and animal data linking developmental exposures to environmental chemicals to various cancers, reproductive diseases, immune dysfunction and diseases, metabolic syndrome, neurobehavioral deficits and abnormalities, and transgenerational effects. In addition, there were discussions on the National Children’s Studies, Clinical and Industry Perspectives, and Regulatory Challenges and Approaches. The session on regulatory challenges focused on the fact that current regulatory protocols and risk assessment methods are poorly equipped to consider latent health impacts of early exposures, especially if they cross generations. Two poster sessions highlighted over 120 abstracts including those of the 38 student travel awardees.
In addition to awarding 41 Student Travel Awards for the PPTOXII meeting, Nicholas E. Heger, Annette M. Herman, Benjamin J. Moyes, Jessica LaRocca, and Michele La Merrill are recipients of the PPTOXII Student Travel Awards for the SOT 2010 Annual Meeting.
It has long been known that development is a sensitive stage for exposures to environmental chemicals due to organogenesis and rapid perinatal growth and the relative lack of active metabolic capacity, DNA repair and brain and testis barriers. However, the discovery that development is the time when epigenetic marks are established that control subsequent gene expression has enhanced the potential impact of this new paradigm of disease etiology. Environmental exposures during development have been reported to increase the rate of birth defects and premature birth can also alter epigenetic markings (DNA methylation and chromatin packaging). As highlighted at the conference, alterations in the epigenetic system can lead to altered gene expression that results in tissues that appear normal but are functionally abnormal due to abnormal gene expression leading to altered signaling pathways. These functional changes then lead to disease and dysfunction over the lifespan long after the exposures are no longer apparent. At present the majority of the data supporting the role of environmental stressors in the developmental origins of disease, as delineated during the workshop, comes from animal studies. Indeed there are data in animal models showing that developmental exposures to numerous chemicals, including bisphenol A, atrazine, phthalates, dioxins, and pcbs, flame retardants, metals, DES, genistein, can result in breast, prostate and uterine cancers, infertility, diabetes/obesity/metabolic syndrome, cognitive and learning disabilities, Parkinson’s and other neurodegenerative diseases as well as cardiopulmonary diseases including asthma and atherosclerosis and hypertension. Human data is presently limited to assessment of childhood disorders including ADHD, asthma, obesity, and cognitive effects as those diseases/dysfunctions can most easily be linked to developmental exposures.
The conference identified numerous data gaps, obstacles, and challenges including the need for more collaboration between animal researchers, epidemiologists, and clinicians; the need for more mechanistic studies showing not just correlations but actual causation, improved exposure measurements in human studies and animal models; the development of banked biospecimans to link developmental exposures to diseases later in life; and the study of mixtures and multiple exposures across the lifespan.
The SOT conference had broad national/international support from a number of agencies including WHO, NIEHS, FDA/NCTR, CDC, ATSDR, NICHD, US EPA, NCI, Superfund Research Program, National Center for Environmental Studies, European Environment Agency, and IUTOX.
The presentations will be published in Toxicological Sciences and the manuscripts will appear in Reproductive Toxicology and the Journal of Developmental Origins of Disease.
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