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

胎盘 RNA 表达与胎龄和环境暴露的关系

基本信息

批准号：
9197555
负责人：
Susan L Schantz
金额：
$ 24.57万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9197555
关键词：
Accounting Address Archives Basic Science Biological Biological Assay Biology Blood Circulation Candidate Disease Gene Cardiovascular Diseases Cells Chemical Exposure Chemicals Chorionic Gonadotropin Collection Conceptus Corticotropin-Releasing Hormone Data Detection Development Developmental Delay Disorders Diethylhexyl Phthalate Disease Endocrine Endocrine Disruptors Endothelial Cells Environment Environmental Epidemiology Environmental Exposure Epidemiologist Exposure to Fetal Growth Retardation Functional disorder Future Gene Expression Genes Genetic Transcription Genomics Gestational Age Goals Health Home environment Hormones Human Human Development Illinois Libraries Life Link Liquid substance Machine Learning Measures Mediating Mental disorders Messenger RNA Metabolic syndrome Methods MicroRNAs Monitor Morbidity - disease rate Mothers Nature Neurodevelopmental Disorder Organ Outcome Outcome Measure Participant Pattern Peptides Placenta Placentation Population Pre-Eclampsia Pregnancy Pregnancy Tests Pregnant Women Premature Birth Premature Labor Procedures RNA Reporting Research Role Sampling Signal Transduction Small RNA Source Spontaneous abortion Stromal Cells Structure Surrogate Markers Syncytiotrophoblast Syndrome Techniques Testing Time Tissues Transcript Urine Uterine cavity Villous abstracting age effect base cell type clinically relevant cohort cytotrophoblast design developmental toxicology extracellular vesicles genome-wide in vivo interest mortality multidisciplinary neonatal morbidity neurodevelopment novel offspring perinatal morbidity personal care products phthalates postnatal prenatal response study population transcriptome transcriptome sequencing urinary

项目摘要

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.

项目概要/摘要胎盘是人类发育的重要器官，破坏它的功能可能导致怀孕问题，包括流产、早产临产、先兆子痫和宫内生长受限。此外，还受到干扰怀孕期间的胎盘功能与许多因素有关直到后代生命很晚的时候才会出现的紊乱和疾病例如代谢综合征、心血管疾病、发育迟缓等其他神经发育和精神疾病。曝光度如何环境中遇到的情况会导致胎盘结构的改变对功能了解甚少，胎盘功能难以在体内评估使用非侵入性方法。我们建议了解基因表达是如何进行的通过非侵入性表征妊娠期间胎盘的改变胎盘转录组与暴露于已知会改变的化学物质有关内分泌信号。这些化学物质称为邻苯二甲酸盐，常见于各种商业产品，例如塑料和个人护理产品，邻苯二甲酸盐暴露也被证明会影响神经发育。这邻苯二甲酸盐暴露与体内胎盘基因表达之间的联系尚不清楚清除;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盐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。该产品的优点之一是拟议的研究是我们将以非侵入性方式评估胎盘基因表达通过细胞外囊泡中含有的RNA分子分泌到孕妇的尿液。收集基因表达数据和化学数据尿液中的暴露数据与临床高度相关，我们期望我们的就像家庭妊娠测试一样，该方法将具有明确的转化应用依赖于检测尿液中胎盘产生的激素已成为常见的。我们提出的研究将为以下方面提供基础科学背景：开发快速、无创的测试来评估胎盘功能，化学品暴露，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。