Epigenetic effects if endocrine disruptors in fetal germ cells

胎儿生殖细胞中内分泌干扰物的表观遗传效应

• 批准号: 7171695
• 负责人: Piroska Edit Szabó
• 金额: $ 42.25万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-22 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171695
• 关键词: DNA methylation; embryo /fetus toxicology; endocrine disrupting compound; epigenetics; functional /structural genomics; gene environment interaction; gene induction /repression; genetic transcription; genomic imprinting; germ cells; laboratory mouse; microarray technology; molecular cloning; nucleic acid sequence; pregnancy

DESCRIPTION (provided by applicant): Some non-genotoxic agents cause epigenetic changes, including aberrant DNA methylation. A subset of these drug, called endocrine disrupters -synthetic chemicals resembling natural hormones-, have profound effects on development and fertility. The central hypothesis of the proposal is that developing germ cells, which undergo genome-wide epigenetic reprogramming, are especially vulnerable to the epigenetic effects of endocrine disrupters. Fetal germ cells provide an excellent study system to reveal the origin of transgenerational epigenetic effects. This proposal seeks to identify epigenetic changes in fetal germ cells after intrauterine exposure to selected endocrine disrupters. To address the central hypothesis, the specific aims are to: 1) Determine the methylation status of the H19/lgf2 imprinting control region (ICR) in perinatal germ cells after fetal exposure to endocrine disrupting chemicals; 2) Assess global transcription changes caused by endocrine disrupters in fetal germ cells and gonadal somatic cells; and 3) Identify targets for aberrant hypermethylation by endocrine disrupters, in mouse female and male germ cells.

描述（由申请人提供）： 一些非遗传毒性剂引起表观遗传变化，包括异常DNA甲基化。这些药物的一个子集，称为内分泌干扰物-类似天然激素的合成化学物质-对发育和生育能力有深远的影响。该提案的核心假设是，发育中的生殖细胞经历全基因组表观遗传重编程，特别容易受到内分泌干扰物的表观遗传影响。胎儿生殖细胞为揭示跨代表观遗传效应的起源提供了一个极好的研究系统。该提案旨在确定胎儿生殖细胞在宫内暴露于选定的内分泌干扰物后的表观遗传变化。为了解决中心假设，具体的目标是：1）确定胎儿暴露于内分泌干扰物后围产期生殖细胞中H19/lgf 2印迹控制区（ICR）的甲基化状态; 2）评估由内分泌干扰物引起的胎儿生殖细胞和性腺体细胞的整体转录变化;和3）鉴定小鼠雌性和雄性生殖细胞中内分泌干扰物引起的异常超甲基化的靶点。