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

• 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
• 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

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 在大量出生数量最多的美国100个城市中，底特律的早产最高 （PTB）15.2％.1目前在公共卫生紧急情况下起着核心作用的病因学因素是 未知。但是，有证据表明暴露于挥发性，非常挥发性和半挥发性有机物 在易感性易受伤害的窗户期间，化合物（统称缩写为VOC）很重要 孕产妇的决定因素，对PTB和相关的不良健康结果有影响。 环境意识与研究领导力中心（清晰）致力于理解 并减轻这种严重的环境健康问题。项目B2的中心主题侧重于 解密信号通路，怀孕期间接触VOC的信号通路会影响早期生活 生长和发育以关注胎儿免疫系统。我们的中心假设是炎症 由于孕产妇暴露于VOC，在胎盘和Decidua中，改变了胎儿的发展 免疫系统，导致对感染的异常产后免疫反应。我们的初步 研究表明，尽管胎儿可能受到微生物感染的保护，但母亲的结果 暴露，保护性或有害的，取决于免疫反应的性质和严重程度 植入部位的炎症过程（胎盘 - decidua界面）。依据的机制 胎儿免疫系统对VOC暴露的反应以及如何通过VOC诱导的母体培训 炎症发生尚不清楚和研究。我们的具体目的是： 目的1。确定BTEX母体暴露对胎盘和胎儿炎症的影响。 目的2。确定voc的影响对负责归宿的TLR信号的影响 T和B细胞的分化。 AIM 3。表征来自有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 胎盘/DECIDUA单位的VOC暴露及其对胎儿编程及其的影响 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）项目之间使用吸入VOC的胎盘模型 接触。化学分析核心将量化BTEX代谢物以及数据管理和分析 核心将在生物医学项目之间传播数据，以进行鱼类，老鼠和 人类可能会暴露范例。 B2将告知未来的流行病学研究，以调查关联 在哮喘等儿童的孕妇VOC暴露和炎症结果之间。