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

总结 流行病学证据表明，父母的环境暴露与 儿童甚至孙辈患慢性病的风险增加。动物研究提供了 明确的证据表明，祖先接触化学品，如内分泌干扰物，二恶英，或 农药可导致几代人的非孟德尔（但可遗传）健康损害。 到目前为止，大多数研究都集中在啮齿动物身上，这对几种化合物施加了限制， 时间在少数动物和统计上健全的实验，涵盖多个 世代需要数年。因此，全面的尝试，以确定化学品能够 完全没有诱发代际效应。重要的是， 通过这种方式，父母接触会导致后代的遗传健康影响， 仍然知之甚少。本项目的目标是：1）开发和验证一种新的 高通量果蝇（Drosophila）模型用于化学品暴露和代际健康 影响，以及2）识别重新编程签名，以帮助揭示潜在的生物学机制 将这些非遗传效应从父母传递给后代。

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.