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

识别能够严重损害几代人健康的环境化学物质

基本信息

批准号：
10371255
负责人：
Heidi Lempradl
金额：
$ 23.75万
依托单位：
VAN ANDEL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10371255
关键词：
Acute Address Animal Model Animals Arsenic Behavioral Biological Blood ChIP-seq Chemical Exposure Chemical Models Chemicals Child Chromatin Chronic Disease Dietary Intervention Dioxins Disease Drosophila genus Embryo Endocrine Disruptors Environmental Exposure Environmental Monitoring Environmental Pollutants Epidemiology Epigenetic Process Exposure to Famines Fathers Fertility Frequencies Future Gene Activation Gene Expression Profile Gene Silencing Generations Genetic Transcription Guidelines Hazardous Chemicals Health Heritability Human Immune Impaired health Individual Knowledge Lead Life Cycle Stages Link Measures Metabolic Methods Modeling Modification Mus Obesity Organism Parents Paternal Exposure Pesticides Phenotype Population Predisposition RNA Reporting Research Risk Rodent Rodent Model Screening procedure Severities Smoking Sweden Testing Time Toxicology Untranslated RNA Urine chromatin modification cohort disease phenotype environmental chemical epidemiology study epigenomics experience experimental study high throughput screening histone modification in vivo insight intergenerational non-genetic novel strategies offspring screening sound sugar trait

项目摘要

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.

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。