Placental RNA Expression as a Function of Gestational Age and Environmental Exposures

项目总结/摘要 胎盘是人类发育的重要器官， 它的功能可能导致怀孕问题，包括流产，早产 分娩、先兆子痫和胎儿宫内生长受限。此外，中断 妊娠期间胎盘功能与大量的 直到后代生命后期才出现的紊乱和疾病 例如代谢综合征、心血管疾病、发育迟缓， 其他神经发育和精神疾病。如何暴露 在环境中遇到的驱动器胎盘结构的改变， 胎盘的功能知之甚少，胎盘功能难以在体内评估 使用非侵入性方法。我们希望了解基因表达是如何 通过非侵入性地表征妊娠期间胎盘中的 胎盘转录组与暴露于化学物质有关 内分泌信号这些化学物质被称为邻苯二甲酸盐，通常存在于 各种商业产品如塑料和个人护理产品， 邻苯二甲酸酯暴露也被证明会影响神经发育。的 邻苯二甲酸酯暴露与体内胎盘基因表达之间的联系尚不清楚 因此，我们组建了一个由神经科学家组成的团队， 胎盘生物学家、环境流行病学家和基因组学专家 解决邻苯二甲酸酯暴露和胎龄如何影响基因 在胎盘中表达，但在其他组织中不表达。的优点之一 一项提议的研究是，我们将评估胎盘基因表达的非侵入性 通过细胞外囊泡中的RNA分子分泌到 孕妇的尿液。收集基因表达数据和化学 尿液中的暴露数据具有高度的临床相关性，我们希望我们的 这种方法将有明确的翻译应用，就像家庭怀孕测试一样。 依靠检测尿液中胎盘产生的激素， 共同我们提出的研究将提供基本的科学背景， 开发快速、非侵入性的测试来评估胎盘功能， 化学暴露，最终导致神经发育和其他方面的问题， 怀孕期间的危险信号

Project Summary/Abstract The placenta is an essential organ in human development, and disruption of its function can result in problems in pregnancy including miscarriage, preterm labor, preeclampsia and intrauterine growth restriction. Additionally, disrupted placenta function during pregnancy has been associated with a great number of disorders and diseases that do not present until much later in the offspring's life such as metabolic syndrome, cardiovascular diseases, developmental delay and other neurodevelopmental and psychiatric disorders. How the exposures encountered in the environment drive alterations in placenta structure and function is poorly understood, and placenta function is difficult to assess in vivo using noninvasive methods. We propose to understand how gene expression is altered in the placenta during gestation by noninvasively characterizing the placenta transcriptome in association with exposure to chemicals known to alter endocrine signaling. These chemicals, called phthalates, are commonly found in a variety of commercial products such as plastics and personal care products, and phthalate exposure has also been shown to effect neurodevelopment. The link between phthalate exposure and placenta gene expression in vivo is not yet clear; therefore we have assembled a team comprised of neuroscientists, placenta biologists, environmental epidemiologists, and genomics experts do address how phthalate exposure and gestational age effects gene that are expressed in the placenta but not in other tissues. One of the advantages of the proposed research is that we will assess placenta gene expression noninvasively through RNA molecules contained in extracellular vesicles that are secreted into the urine of pregnant women. Collecting gene expression data and chemical exposure data from urine is highly clinically relevant, and we expect our approach will have clear translational applications just as home pregnancy tests that rely on the detection of placenta produced hormones in urine have become common. Our proposed study will provide the basic science background for the development of rapid, noninvasive tests for assessing placenta function, chemical exposures, and ultimately problems in neurodevelopment and other danger signals during pregnancy.