Identification of environmental chemicals capable of inducing health impairments acutely and across generations

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SUMMARY Epidemiological evidence suggests that parental environmental exposure correlates with increased risk of chronic diseases in children and even grandchildren. Animal studies provide clear evidence that ancestral exposure to chemicals such as endocrine disruptors, dioxins, or pesticides can induce non-Mendelian (but heritable) health impairments across generations. Most research thus far has focused on rodents, which imposes limits of a few compounds at a time in small numbers of animals and statistically sound experiments covering multiple generations require years. Thus, comprehensive attempts to identify chemicals capable of inducing intergenerational effects have been completely lacking. Importantly, the mechanisms by which parental exposure leads to heritable health effects in subsequent generations are still poorly understood. The objectives of this project are to 1) develop and verify a new high-throughput fruit fly (Drosophila) model for chemical exposure and intergenerational health effects, and 2) identify reprograming signatures to help uncover potential biological mechanisms for transmitting those non-genetic effects from parent to offspring.