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Animal Models for Testing the DOHaD Hypothesis
Citation:
ROGERS, J. M. Animal Models for Testing the DOHaD Hypothesis. Presented at Society of Toxicology-PPTOXII: Role of Environmental Stressors in the Developmental Origins of Disease Meeting, Miami, FL, December 07 - 10, 2009.
Impact/Purpose:
Present overview of animal models to study the effects of developmental exposures to chemicals on adult health.
Description:
Since the seminal work in human populations by David Barker and colleagues, several species of animals have been used in the laboratory to test the Developmental Origins of Health and Disease (DOHaD) hypothesis. Rats, mice, guinea pigs, sheep, pigs and non-human primates have been used to tests aspects of the DOHaD hypothesis, and each offers different advantages due to size, length of gestation, availability of genetic tools, type of placentation, or physiological similarity to humans. To date, experimental models of developmental programming have included various forms of prenatal and/or early postnatal under-or malnutrition, maternal glucocorticoid exposure, maternal stress, maternal care, or intrauterine growth restriction induced by uterine ischemia (Le., vascular clamping) or overcrowding of a uterine horn in rodents. Effects of environmental toxicants on developmental programming are beginning to be discovered, with emphasis on endocrine disrupting chemicals. In addition, some insights have been gained by the study of cloned offspring of various species. Endpoints studied in offspring include components of the metabolic syndrome (obesity, insulin resistance, glucose intolerance, elevated blood pressure, dyslipidemia), reproductive physiology and behavior, learning, stress response, cancer, immunology and multigenerational effects. The physiological underpinnings of these apical outcomes have been elucidated to varying degrees, and epigenetic studies are just beginning. Comparing and synthesizing results across laboratory species and extrapolation to humans requires an understanding of their different gestational strategies, nutritional requirements, growth trajectories, and physiologies. Species and strain differences in response to environmental influences during development are poorly understood at present. This talk will survey extant animal models, experimental approaches and comparative outcomes, and implications for regulatory testing and human risk assessment. This . abstract does not reflect EPA policy.