Project C: Epigenetic Effects of DDT/E and PBDEs on Puberty

项目 C：DDT/E 和 PBDEs 对青春期的表观遗传影响

• 批准号: 8185133
• 负责人: Nina T Holland
• 金额: $ 15.09万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8185133
• 关键词: 12 year old; 3 year old; 7 year old; 9 year old; Adverse effects; Affect; Age; Age of Onset; Age-Years; Aging; Agriculture; Air Pollution; Animal Model; Area; Benzene; Biological; Biological Assay; Biological Markers; Biological Process; Birth; Blood; California; Cells; Child; Child health care; Collection; Communities; Cytosine; DNA; DNA Methylation; DNA Modification Process; DNA Sequence; Data; Development; Disease; Electronics; Endocrine Disruptors; Endocrine disruption; Enrollment; Environmental Exposure; Environmental Health; Enzymes; Epigenetic Process; Exposure to; Fertility; Flame Retardants; Funding; Furniture; Gene Expression; Genes; Genetic; Genetic Transcription; Global Change; Growth; Guanosine; Health; Hormonal Change; Hormones; Household; Human; Human Cell Line; Individual; Integration Host Factors; Lead; Life; Malignant Neoplasms; Maternal Exposure; Methodology; Methylation; Mexican; Mexico; Minority; Modification; Mothers; Newborn Infant; Outcome; Pattern; Persons; Phenotype; Play; Policies; Pollution; Predisposition; Pregnancy; Pregnant Women; Puberty; Recording of previous events; Research; Role; Sample Size; Sampling; Serum; Shapes; Site; Testing; Textiles; Time; Toxic Environmental Substances; Training; Validation; Variant; Woman; base; boys; cohort; dichlorodiphenyltrichloroethane; early life exposure; farm worker; fetal blood; follow-up; genome-wide; girls; in utero; methyl group; neurodevelopment; organochlorine pesticide; phenyl ether; pollutant; postnatal; prenatal; sex; toxicant; trafficking

Epigenetic markers are heritable changes in phenotype or gene expression in the absence of changes in DNA sequence. DNA methylation, the most common type of epigenetic modification, plays an important role in cancer, aging, neurodevelopment, and fertility. Recently, changes in global methylation in blood DNA have been associated with environmental exposures, including exposure to persistent organic pollutants, benzene, and air pollution. Little is known about DNA methylation in children, including variations with sex or age and associations with health endpoints or environmental exposures. In this proposal, we will determine whether pre- and/or postnatal exposures to DDT/E and PBDEs, persistent endocrine-disrupting toxicants, are related to global and site-specific DNA methylation in fetal blood and blood of 9-year-old children. We will also determine whether DNA methylation is related to the timing of puberty onset. Ultimately, we aim to identify specific genetic regions where epigenetic modifications can be used as biomarkers of exposure or abnormal pubertal development. We will use the rich collection of biological samples, exposure information, and health outcome data collected by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal birth cohort of 601 women and children with demonstrated high exposure to DDT/E and PBDEs. In this cohort, we will: 1) analyze global DNA methylation in newborn children by pyrosequencing of Alu and LINE-1 repeats, and Infinium Methylation assay; 2) determine ontogenetic changes in global methylation in children at birth, 1, 5, 9, and 12 years of age; 3) determine the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global methylation; 4) determine whether global DNA methylation is associated with onset of puberty and hormonal changes; and 5) examine genome-wide site-specific methylation in relation to age, sex, exposure to DDT/E and PBDEs and puberty onset. The total sample size will be 250 children with blood available at birth and 9 years of age. Aims 1, 3, 4 and 5 will be comprised of 100 randomly selected children in a Discovery set and 150 children in a Replication set. Aim 2 will include a subset of 50 children with blood also at 1, 5, and 12 years of age. Epigenetic markers may be a key mechanism by which environmental exposures affect children's health. This study will provide some of the first data on the ontogeny of epigenetic changes in children and their association with environmental exposures and developmental outcomes.

表观遗传标记是在没有变化的情况下表型或基因表达的可遗传变化。 DNA 序列。 DNA 甲基化是最常见的表观遗传修饰类型，发挥着重要作用 在癌症、衰老、神经发育和生育方面。最近，血液 DNA 中整体甲基化的变化 与环境暴露有关，包括接触持久性有机污染物， 苯和空气污染。人们对儿童 DNA 甲基化知之甚少，包括性别或性别差异 年龄以及与健康终点或环境暴露的关联。 在本提案中，我们将确定产前和/或产后是否接触 DDT/E 和 PBDE， 持久性内分泌干扰毒物，与胎儿体内整体和位点特异性 DNA 甲基化有关 9岁儿童的血和血。我们还将确定 DNA 甲基化是否与 青春期开始的时间。最终，我们的目标是确定表观遗传修饰发生的特定遗传区域 可用作暴露或青春期发育异常的生物标志物。我们将利用丰富的收藏 卫生中心收集的生物样本、暴露信息和健康结果数据 萨利纳斯母亲和儿童评估 (CHAMACOS) 研究，一项包含 601 名纵向出生队列的研究 大量接触 DDT/E 和 PBDE 的妇女和儿童。在这个队列中，我们将：1) 通过 Alu 和 LINE-1 重复序列的焦磷酸测序分析新生儿的整体 DNA 甲基化，以及 Infinium 甲基化测定； 2) 确定儿童出生时整体甲基化的个体发生变化，1, 5, 9岁、12岁； 3) 确定子宫内和9岁儿童血液浓度的关系 具有全局甲基化的 DDT/E 和 PBDEs； 4) 确定全局DNA甲基化是否与 青春期的开始和荷尔蒙的变化； 5) 检查与以下相关的全基因组位点特异性甲基化 年龄、性别、接触 DDT/E 和 PBDE 以及青春期开始时间。样本总数为 250 名儿童 出生时和 9 岁时可获得血液。目标 1、3、4 和 5 将由 100 个随机选择的项目组成 发现集中有 150 个子级，复制集中有 150 个子级。目标 2 将包括 50 名儿童 1、5 和 12 岁时也有血液。 表观遗传标记可能是环境暴露影响儿童健康的关键机制。 这项研究将提供一些关于儿童及其表观遗传变化的个体发育的首批数据。 与环境暴露和发育结果的关联。