Project 2: Investigating the role of PAH exposures associated with superfund site proximity in preterm birth etiology through placental transcriptomics and metagenomics

项目 2：通过胎盘转录组学和宏基因组学研究与超级基金地点邻近相关的 PAH 暴露在早产病因学中的作用

• 批准号: 10116393
• 负责人: Kjersti Marie Aagaard
• 金额: $ 24.47万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-28 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10116393
• 关键词: Aromatic Polycyclic Hydrocarbons; Automobile Driving; Biological Assay; Biological Markers; Body mass index; Cells; Chemicals; Chronic lung disease; Clinical; Collaborations; County; DNA Adducts; DNA Methylation; Data; Detection; Dose; Environmental Exposure; Ethnic Origin; Etiology; Exposure to; Gene Expression; Geographic Information Systems; Gestational Age; In Vitro; Maps; Mass Fragmentography; Maternal Age; Maternal and Child Health; Measurable; Measures; Mediating; Metagenomics; Methods; Modeling; Molecular; Monitor; Morbidity - disease rate; Neurocognitive Deficit; Outcome; Perinatal mortality demographics; Phase; Placenta; Predisposition; Pregnancy; Pregnant Women; Premature Birth; Prevention; Prospective cohort; Race; Reporting; Research; Retrospective cohort; Rice; Risk; Role; Sampling; Serum; Signal Recognition Particle; Silicones; Smoking; Soil; Solid; Term Birth; Third Pregnancy Trimester; Time; Tissues; Very Low Birth Weight Infant; Woman; adduct; adverse pregnancy outcome; base; cohort; comorbidity; early life exposure; epigenomics; experimental study; genome sciences; genome-wide; improved; information system analysis; insight; monitoring device; mortality; perinatal morbidity; population based; recruit; remediation; residence; superfund site; transcriptome sequencing; transcriptomics; trophoblast

The burden of perinatal morbidity and mortality related to preterm birth (PTB) is astounding. Studies show that environmental exposures contribute to an increased susceptibility to PTB. Identification of the causative etiology of PTB is essential to improving global maternal and child health. Our preliminary data reveal that exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with PTB. We have reported that proximity to Superfund sites in Harris County is associated with very low birth weight, and our studies reveal higher levels of PAHs in placentas from PTBs compared to term births specifically in women residing near Superfund sites. In this proposal we will delve into the molecular underpinnings behind PTB and the specific environmental exposures of PAHs through use of our established transcriptomic and epigenomic pipelines. We will leverage our readily available serum and placental samples from a population based and PTB enriched cohort. Furthermore, geostatistical modeling will be utilized to identify clusters of PTB throughout Harris County. Our central hypothesis underlying our research is that PAH exposures are associated with an increased rate of PTB, that transcriptomics and epigenomics will yield readily translatable mechanistic information on this association, and geostatistical modeling will reveal increased clusters of PTB in proximity to Superfund sites in Harris County.

与早产 (PTB) 相关的围产期发病率和死亡率的负担令人震惊。研究表明 环境暴露会增加对 PTB 的易感性。识别病因 PTB 的病因学对于改善全球孕产妇和儿童健康至关重要。我们的初步数据表明 接触多环芳烃 (PAH) 与 PTB 相关。我们已经报告过，接近 哈里斯县的超级基金地点与极低的出生体重有关，我们的研究表明， 与足月分娩相比，PTB 胎盘中的 PAH 水平，特别是居住在 Superfund 附近的妇女 网站。在本提案中，我们将深入研究 PTB 背后的分子基础以及具体的 通过使用我们已建立的转录组和表观基因组管道来检测多环芳烃的环境暴露。我们 将利用我们现成的血清和胎盘样本，这些样本来自基于人群且富含 PTB 的样本 队列。此外，地质统计模型将用于识别整个哈里斯地区的 PTB 集群 县。我们研究的中心假设是，PAH 暴露与 PTB 率增加，转录组学和表观基因组学将产生易于翻译的机制 有关此关联的信息，并且地质统计模型将揭示附近 PTB 集群的增加 哈里斯县的超级基金地点。