Impact of BTEX Chemical Exposure During Pregnancy to Maternal and Fetal Well-Being

怀孕期间接触 BTEX 化学品对母亲和胎儿健康的影响

基本信息

批准号：
10352965
负责人：
GIL G MOR
金额：
$ 31.2万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-08 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10352965
关键词：
Address Affect Air Pollutants American Area Asthma Awareness B-Lymphocytes Benzene Biological Biomedical Research Birth Birth Rate Chemical Exposure Chemicals Child Chronic Disease Cities Clinical Communicable Diseases Communities Consultations Data Data Analyses Decidua Development Dose Environmental Engineering technology Environmental Health Epidemiology Etiology Exposure to Fetal Development Fetal Growth Retardation Fetus Fishes Future Growth Growth and Development function Health Homing Household Human Immune Immune response Immune system Incidence Industrialization Infant Infection Inflammation Inflammatory Inhalation Inhalation Exposure Leadership Life Link Liver Maternal Exposure Methods Modeling Modification Molecular Mothers Mus Nature Neonatal Newborn Infant Occupational Outcome Pathogenesis Personal Satisfaction Phenotype Placenta Plant Roots Play Pre-Eclampsia Predisposition Pregnancy Pregnancy Complications Premature Birth Process Property Receptor Signaling Reporting Research Risk Role Severities Signal Pathway Site Soil Superfund System T cell differentiation T-Lymphocyte Techniques Technology Testing Thymus Gland Toll-like receptors Toluene Toxic effect Training Vaccines Viral Xylene Zebrafish biological systems community engagement data management epidemiology study ethylbenzene exposed human population fetal fetal programming ground water immune activation implantation improved in utero maternal morbidity maternal outcome microbial microorganism mortality mouse model neonatal morbidity neonate offspring preclinical study prenatal exposure programs public health emergency public health intervention pup response stressor superfund site urban area vapor intrusion volatile organic compound

项目摘要

Abstract Among the 100 American cities with the greatest number of births, Detroit has the highest reported preterm birth (PTB) rate of 15.2%.1 The etiologic factors that play central roles in this public health emergency are currently unknown. However, evidence suggests that exposure to volatile, very volatile, and semi-volatile organic compounds (collectively abbreviated VOCs) during vulnerable life windows of susceptibility is an important determinant of maternal-offspring health, with implications for PTB and associated adverse health outcomes. The Center for Leadership in Environmental Awareness and Research (CLEAR) is dedicated to understanding and mitigating this serious environmental health problem. The central theme of Project B2 focuses on deciphering the signaling pathways by which exposure to VOCs during pregnancy have an impact on early life growth and development with a focus on the fetal immune system. Our central hypothesis is that inflammation in the placenta and decidua due to maternal exposure to VOCs, alters the development of the fetal immune system, which results in an aberrant post-natal immune response to infections. Our preliminary studies suggest that although the fetus may be protected against microbial infection, the outcome of maternal exposure, protective or deleterious, depends on the nature of the immune response and the severity of the inflammatory process at the implantation site (placenta-decidua interface). The mechanisms underlying the response of the fetal immune system to VOC exposure and how indirect training by VOC-induced maternal inflammation takes place is unclear and understudied. Our specific aims are: Aim 1. To determine the effect of BTEX maternal exposure on placental and fetal inflammation. Aim 2. To determine the impact of VOCs exposure on TLR signaling responsible for the homing and differentiation of T and B cells. Aim 3. Characterize the offspring immune responses of pups from mothers with VOCs exposure to microbial infection. Upon completion of these aims we will have a better understanding of the outcomes associated with the impact of VOCs exposure on the placental/decidua unit and its consequent influence on fetal programing and its potential effects on the development of an appropriate neonatal immune responses. B2 is a mechanistic bridge between the zebrafish (B1) and epidemiological (B3) projects that utilizes a placental model of inhalational VOC exposure. The Chemical Analysis Core will quantitate BTEX metabolites and the Data Management and Analysis Core will disseminate data among the biomedical projects to make comparisons between fish, mouse, and human exposures paradigms possible. B2 will inform future epidemiological studies that investigate associations between maternal VOC exposures and inflammatory outcomes in children such as asthma.

抽象的在美国出生人数最多的100个城市中，底特律早产率最高 (PTB) 率为 15.2%。1 目前在本次突发公共卫生事件中起核心作用的病因是未知。然而，有证据表明，接触挥发性、极挥发性和半挥发性有机物化合物（统称为 VOC）在脆弱生命窗口期间的易感性是一个重要的母子健康的决定因素，对 PTB 和相关的不良健康结果具有影响。环境意识与研究领导力中心 (CLEAR) 致力于了解并缓解这一严重的环境健康问题。 B2项目的中心主题集中于破译怀孕期间接触挥发性有机化合物对早期生命产生影响的信号通路生长和发育，重点关注胎儿免疫系统。我们的中心假设是炎症由于母体接触挥发性有机化合物，胎盘和蜕膜中的有害物质会改变胎儿的发育免疫系统，导致产后对感染的异常免疫反应。我们的初步研究表明，虽然胎儿可以免受微生物感染，但母体的结局接触，无论是保护性的还是有害的，取决于免疫反应的性质和严重程度植入部位（胎盘-蜕膜界面）的炎症过程。其背后的机制胎儿免疫系统对 VOC 暴露的反应以及 VOC 诱导的母亲如何进行间接训练炎症的发生尚不清楚且尚未得到充分研究。我们的具体目标是：目标 1. 确定母体接触 BTEX 对胎盘和胎儿炎症的影响。目标 2. 确定 VOC 暴露对负责归巢和归巢的 TLR 信号传导的影响 T 细胞和 B 细胞的分化。目标 3. 表征暴露于 VOC 的母亲的幼崽的后代免疫反应微生物感染。完成这些目标后，我们将更好地了解与影响相关的结果 VOCs 暴露对胎盘/蜕膜单位的影响及其对胎儿编程及其后果的影响对适当的新生儿免疫反应的发展的潜在影响。 B2是机械桥斑马鱼 (B1) 和流行病学 (B3) 项目之间利用吸入 VOC 的胎盘模型接触。化学分析核心将定量 BTEX 代谢物以及数据管理和分析 Core 将在生物医学项目之间传播数据，以对鱼、小鼠和动物进行比较人类暴露范例成为可能。 B2 将为未来调查关联的流行病学研究提供信息母亲VOC暴露与儿童炎症结果（例如哮喘）之间的关系。