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: 10559699
• 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/10559699
• 关键词: Aromatic Polycyclic Hydrocarbons; Automobile Driving; Biological Assay; Biological Markers; Body mass index; Cells; Chemicals; Chronic lung disease; Clinical; Collaborations; County; DNA Adduction; DNA Adducts; DNA Methylation; Data; Detection; Dose; Environmental Exposure; Ethnic Origin; Etiology; Exposure to; Gene Expression; Geographic Information Systems; Gestational Age; In Vitro; Label; 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; 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.

与早产有关的围产期发病率和死亡率的负担是惊人的。研究表明 环境暴露导致对PTB的易感性增加。确定原因 PTB的病因学对于改善全球孕产妇和儿童健康至关重要。我们的初步数据显示， 接触多环芳烃与肺结核有关。我们已经报道过， 哈里斯县的超级基金网站与非常低的出生体重有关，我们的研究显示， 与足月分娩相比，PTB胎盘中的多环芳烃水平，特别是居住在超级基金附近的妇女 网站.在这个建议中，我们将深入研究PTB背后的分子基础和具体的 通过使用我们已建立的转录组学和表观基因组学管道，减少环境中的多环芳烃暴露。我们 将利用我们现有的血清和胎盘样本，这些样本来自于基于人群和富含PTB的 队列。此外，将利用地统计建模来识别整个哈里斯的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， 关于这种关联的信息和地质统计学建模将揭示， 哈里斯县的超级基金网站。