Environment, Fetal Tissue DNA Methylation & Birthweight

环境、胎儿组织 DNA 甲基化

• 批准号: 8153574
• 负责人: Andrea Baccarelli
• 金额: $ 91.05万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8153574
• 关键词: Address; Adopted; Air Pollution; Archives; Biological; Biological Markers; Birth; Blood; Blood Vessels; Boston; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chemical Exposure; Child; Child Development; Chronic Disease; Cities; Cohort Studies; DNA; DNA Methylation; Data; Disease; Elderly; Enrollment; Ensure; Environment; Environmental Exposure; Environmental Risk Factor; Environmental Tobacco Smoke; Epigenetic Process; Excretory function; Exposure to; Fetal Growth; Fetal Growth Retardation; Fetal Tissues; Fetus; Genes; Genomics; Growth; Health; Human; Infant; Intervention; Knowledge; Lead; Life; Link; Literature; Low Birth Weight Infant; Measures; Mediating; Mediation; Mediator of activation protein; Methylation; Mexico; Mothers; Newborn Infant; Nutrient; Obesity; Operative Surgical Procedures; Organ; Outcome; Pathway interactions; Perinatal; Placenta; Plant Roots; Population; Positioning Attribute; Pregnancy; Process; Program Development; Public Health; Research; Research Infrastructure; Risk; Risk Factors; Role; Sampling; Site; Staging; Stress; Structure of umbilical artery; Testing; Tissues; Toxic Environmental Substances; Umbilical Blood; Umbilical Cord Blood; Umbilical cord structure; Umbilical vein; Vascular System; Waste Products; Work; base; case control; cohort; design; epigenomics; fetal; fetal blood; fetal programming; insight; intergenerational; lead exposure; neurotoxicology; premature; prenatal; programs; prospective; psychosocial; social stress; stressor; toxicant

DESCRIPTION (provided by applicant): Previous studies on impaired fetal growth have identified multiple risk factors including environmental tobacco smoke (ETS), social stress, lead exposure and air pollution. In parallel, a growing body of literature has demonstrated that all 4 of these risk factors can alter DNA methylation, suggesting a common pathway by which such environmental factors impair fetal growth. The key to understanding the role of environment in impairing fetal growth is to 1) measure environmental risk factors prospectively in pregnancy, to ensure that exposure and subsequent epigenetic changes are temporally associated and 2) to measure epigenetic changes in the correct target tissues. While a case control design may be more efficient, such a design could not tease out whether methylation changes were due to environmental factors or were constitutive in impaired growth. This point is critical as reducing risk by intervening on environmental factors requires knowledge of their mechanisms. To this end, this proposal will utilize the existing infrastructure of the ELEMENT birth cohort study in Mexico and a second ongoing study of similar design in Boston-PRISM. ELEMENT and PRISM have archived umbilical cord vessels and placenta as well as ETS, stress, air pollution and lead exposure measured prospectively beginning in the early 2nd trimester and data on fetal growth. We are therefore uniquely positioned to address these important questions. In this proposal, we hypothesize that common environmental risk factors that impair fetal growth will alter methylomic marks in target tissues critical for fetal growth. Fetal growth depends on maternal transport of nutrients as well as the transport and excretion of toxicants and waste products. Logical target tissues for fetal growth would be tissues of the vascular system (vessels, blood and placenta). Perhaps the greatest strength of our proposal is that we can assess multiple "target tissues" and can compare and contrast 450,000 unique methylation sites across these tissues in the context of environmental exposures. This study will make substantial contributions to our understanding the role of environment in fetal growth. PUBLIC HEALTH RELEVANCE: This project will identify DNA methylation alterations in umbilical vessels, placenta and fetal blood that are induced by exposure to environmental tobacco smoke, social stress, lead and air pollution. By conducting analyses on multiple tissues relevant to fetal growth, it will contribute to establishing how different exposures and tissues contribute to fetal growth.

描述（由申请人提供）：先前关于胎儿生长受损的研究已经确定了多种风险因素，包括环境烟草烟雾（ETS）、社会压力、铅暴露和空气污染。与此同时，越来越多的文献表明，所有这4种风险因素都可以改变DNA甲基化，这表明这些环境因素损害胎儿生长的共同途径。了解环境在损害胎儿生长中的作用的关键是：1）在妊娠期前瞻性地测量环境风险因素，以确保暴露和随后的表观遗传变化在时间上相关; 2）测量正确靶组织中的表观遗传变化。虽然病例对照设计可能更有效，但这种设计无法梳理出甲基化变化是由于环境因素还是生长受损的组成性因素。这一点至关重要，因为通过干预环境因素来降低风险需要了解其机制。为此，该提案将利用墨西哥ELEMENT出生队列研究的现有基础设施和波士顿PRISM正在进行的第二项类似设计研究。ELEMENT和PRISM已经将脐带血管和胎盘以及ETS、压力、空气污染和铅暴露存档，这些数据是从妊娠早期开始前瞻性测量的，以及关于胎儿生长的数据。因此，我们处于处理这些重要问题的独特地位。在这个建议中，我们假设，常见的环境危险因素，损害胎儿的生长将改变甲基化标记的目标组织的胎儿生长的关键。胎儿的生长取决于母体对营养物质的运输以及有毒物质和废物的运输和排泄。胎儿生长的合理靶组织是血管系统组织（血管、血液和胎盘）。也许我们的建议最大的优势是，我们可以评估多个“靶组织”，并可以在环境暴露的背景下比较和对比这些组织中的450，000个独特的甲基化位点。这项研究将为我们理解环境在胎儿生长中的作用做出实质性贡献。 公共卫生相关性：该项目将确定暴露于环境烟草烟雾，社会压力，铅和空气污染引起的脐带血管，胎盘和胎儿血液中的DNA甲基化改变。通过对与胎儿生长相关的多种组织进行分析，将有助于确定不同的暴露和组织如何促进胎儿生长。