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: 8304374
• 负责人: Nina T Holland
• 金额: $ 14.87万
• 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/8304374
• 关键词: 12 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; Salinum; 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遗传变化 DNA序列。 DNA甲基化是最常见的表观遗传修饰类型，起着重要作用 在癌症中，衰老，神经发育和生育能力。最近，血液DNA中全球甲基化的变化已 与环境暴露有关，包括暴露于持续的有机污染物， 苯和空气污染。关于儿童的DNA甲基化知之甚少，包括性别的变化或 与健康终点或环境暴露的年龄和关联。 在此提案中，我们将确定出生前和/或出生后是否向DDT/E和PBDES暴露， 持续的内分泌毒性毒物与胎儿中的全球和特定位点DNA甲基化有关 9岁儿童的血液和血液。我们还将确定DNA甲基化是否与 青春期发作的时机。最终，我们旨在确定表观遗传修饰的特定遗传区域 可以用作暴露或异常的青春期发育的生物标志物。我们将使用丰富的收藏 健康中心收集的生物样品，暴露信息和健康结果数据 评估萨利纳斯（Chamacos）研究的母亲和子女，纵向出生队列601 妇女和儿童表现出高暴露于DDT/E和PBDES。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全球DNA甲基化，以及 无甲基化测定法； 2）确定出生时儿童全球甲基化的个体发生变化，1，5， 9岁和12岁； 3）确定子宫内的关系和9岁的血液浓度的关系 DDT/E和PBDE具有全球甲基化； 4）确定全局DNA甲基化是否与 青春期和荷尔蒙变化的发作； 5）检查与全基因组分子特异性甲基化相对于 年龄，性别，暴露于DDT/E和PBDES以及青春期发作。总样本量将为250名儿童 出生时可用的血液和9岁。目标1、3、4和5将由100个随机选择 发现套装的孩子和150个复制套装的孩子。 AIM 2将包括50个孩子的子集 血液也在1、5和12岁时。 表观遗传标记可能是环境暴露会影响儿童健康的关键机制。 这项研究将提供一些有关儿童表观遗传变化及其表观遗传变化及其的首批数据 与环境暴露和发展成果相关。