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

摘要 在出生人数最多的100个美国城市中，底特律的早产率最高 (PTB)发病率为15.2%。1目前，在此次突发公共卫生事件中发挥核心作用的病因是 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（统称为挥发性有机化合物）在脆弱的生命窗口的敏感性是一个重要的 母婴健康的决定因素，与PTB和相关的不良健康结果的影响。 环境意识和研究领导中心（CLEAR）致力于了解 减轻这一严重的环境健康问题。项目B2的核心主题是 解读怀孕期间暴露于VOCs对早期生活产生影响的信号通路 生长和发育，重点是胎儿免疫系统。我们的核心假设是炎症 由于母体暴露于VOC，胎盘和蜕膜中的VOC会改变胎儿的发育 免疫系统，导致出生后对感染的异常免疫反应。我们的初步 研究表明，虽然胎儿可能受到保护，免受微生物感染， 暴露，保护性或有害的，取决于免疫反应的性质和严重性， 着床部位（胎盘-蜕膜界面）的炎症过程。的作用机制 胎儿免疫系统对VOC暴露的反应以及VOC诱导的母体如何间接训练 炎症的发生是不清楚和研究不足。我们的具体目标是： 目标1.确定BTEX母体暴露对胎盘和胎儿炎症的影响。 目标2.确定VOCs暴露对TLR信号传导的影响，TLR信号传导负责归巢， T和B细胞的分化。 目标3：描述暴露于VOCs的母鼠的幼崽的免疫反应， 微生物感染 在完成这些目标后，我们将更好地了解与影响相关的结果 挥发性有机化合物暴露对胎盘/蜕膜单位的影响及其对胎儿编程的影响 对新生儿免疫反应的潜在影响。B2是一座机械桥 斑马鱼（B1）和流行病学（B3）项目之间的关系，该项目利用吸入性VOC的胎盘模型 exposure.化学分析核心将定量BTEX代谢物，数据管理和分析 核心将在生物医学项目中传播数据，以比较鱼类、小鼠和 人类接触的范例可能。B2将为未来的流行病学研究提供信息， 母亲VOC暴露与儿童炎症结局（如哮喘）之间的关系。

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.