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

摘要 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，祖先接触到的化学物质，如内分泌干扰物、二恶英或 杀虫剂可能会导致代代相传的非孟德尔式(但可遗传)的健康损害。 到目前为止，大多数研究都集中在啮齿动物身上，这就限制了一次使用几种化合物。 在少量动物中的时间和统计上可靠的实验涵盖了 世世代代需要数年时间。因此，全面尝试识别能够 诱导代际效应是完全缺乏的。重要的是，这些机制 通过父母的暴露导致后代可遗传的健康影响 人们对此仍然知之甚少。该项目的目标是：1)开发和验证一个新的 高通量果蝇(果蝇)化学暴露与代际健康模型 影响，以及2)识别重新编程签名，以帮助发现潜在的生物机制 将这些非遗传效应从父母传给后代。

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.