Chemical-nonchemical interactions in pregnancy: Animal models of how maternal stress, diet, and obesity affect response to chemical exposure
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Experiments testing the toxicity of chemical exposures in pregnancy typically use nulliparous rodents or rabbits of optimum age and health, of very similar if not identical genotype, that are fed optimum diets and housed in carefully controlled environments. Clearly, this does model the wide variations in all these factors in the human population that we seek to protect from harm. While it is impossible to model all these factors in a single experiment, there is a growing literature on the effects of intrinsic and modifiable factors that influence the outcome of a toxic exposure. Common modifiable factors in humans include maternal diet, obesity, and stress. Co-exposures to toxicants like air pollution and secondhand tobacco smoke during pregnancy are common and can increase risk of health effects in offspring. An adverse in utero environment contributes to shaping the epigenome of the child in ways that can raise the risk of disease later in life and may increase susceptibility to later exposures. Maternal smoking is an example that has been well studied in humans. Umbilical cord blood from infants born to smoking mothers show consistent epigenetic changes that persist at least to adolescence if not throughout life. Offspring of smoking mothers show increased risk of asthma, obesity and diabetes. Multiple studies in humans and animal models have shown that poor maternal diet or undernutrition during pregnancy can cause epigenetic changes that are associated with adverse health outcomes later in life. Maternal obesity predisposes offspring to metabolic disorders and recent studies link paternal obesity to epigenetic alterations. Studies at EPA demonstrated that feeding female rats a high fat diet before and through pregnancy and lactation resulted in increased sensitivity to ozone in adult offspring. Few studies have examined the effects of epigenetic changes on response to pollutant exposures later in life, or strategies to mitigate latent disease risk. This talk will cover selected findings and will include ongoing work to test interactions of modifiable factors with chemical exposures in pregnant rodents.