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.

概括流行病学证据表明，父母的环境暴露与儿童甚至孙子的慢性疾病风险增加。动物研究提供明确的证据表明，祖先接触化学物质，例如内分泌破坏者，二恶英或农药可以诱导几代人的非孟德尔（但可遗传）的健康障碍。到目前为止少数动物和统计声音实验的时间涵盖了多个几代人需要数年。因此，综合尝试识别能够的化学物质完全缺乏诱导代际效应。重要的是，机制父母的暴露会导致随后几代人的可遗传健康影响仍然很了解。该项目的目标是1）开发和验证新的用于化学暴露和代际健康的高通量果蝇（果蝇）模型效果和2）确定重编程特征以帮助发现潜在的生物学机制将这些非遗传效应从父母传播到后代。