Environment, Fetal Tissue DNA Methylation & Birthweight

环境、胎儿组织 DNA 甲基化

• 批准号: 8334545
• 负责人: Andrea Baccarelli
• 金额: $ 90.07万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334545
• 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

7. PROJECT SUMMARY / ABSTRACT 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.

7.项目总结/摘要 以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。在 同时，越来越多的文献表明，所有这4个风险因素都可能 改变DNA甲基化，这表明这种环境影响的共同途径， 影响胎儿生长的因素。理解环境在损害中的作用的关键 胎儿生长是为了1）在怀孕期间前瞻性地测量环境风险因素， 确保暴露和随后的表观遗传变化在时间上相关 和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，这样的设计不能梳理出甲基化是否 变化是由于环境因素或在受损的生长组成。这 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，本提案将利用现有的 墨西哥ELEMENT出生队列研究的基础设施和正在进行的第二项研究 类似的设计。ELEMENT和PRISM已存档脐带缆 血管和胎盘以及ETS，压力，空气污染和铅暴露测量 从孕早期开始前瞻性地观察，并提供胎儿生长的数据。我们 因此，在解决这些重要问题方面具有独特的地位。在本提案中，我们 假设损害胎儿生长的常见环境危险因素将改变 在对胎儿生长至关重要的靶组织中的甲基化标记。胎儿的生长取决于 母体运输营养物质以及运输和排泄有毒物质， 废物。胎儿生长的合理靶组织是血管组织， 系统（血管、血液和胎盘）。也许我们的提议最大的优点是 我们可以评估多个“靶组织”，并可以比较和对比45万个 在环境暴露的背景下，这些组织中的独特甲基化位点。 这项研究将为我们理解 胎儿生长的环境