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：
9341310
负责人：
Susan L Schantz
金额：
$ 19.11万
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 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9341310
关键词：
Address Archives Basic Science Biological Biological Assay 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 Discipline of obstetrics Disease Endocrine Endocrine Disruptors Endothelial Cells Environment Environmental Epidemiology Environmental Exposure Environmental Impact 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 Placental Biology Placentation Plasticizers Plastics 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 age effect 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 prospective 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.

项目摘要/摘要胎盘是人类发展的重要器官，并破坏它的功能可能导致怀孕问题，包括流产，早产劳动，子痫前期和子宫内生长限制。另外，被破坏了怀孕期间的胎盘功能与大量直到后代一生中很久以后才出现的疾病和疾病例如代谢综合征，心血管疾病，发育延迟和其他神经发育和精神疾病。如何暴露在环境中遇到的胎盘结构和功能知之甚少，胎盘功能很难在体内评估使用无创方法。我们建议了解基因表达如何通过非侵入性表征妊娠期间胎盘的改变胎盘转录组与已知改变的化学物质有关内分泌信号传导。这些化学物质（称为邻苯二甲酸盐）通常在各种商业产品，例如塑料和个人护理产品，邻苯二甲酸酯的暴露也已显示为神经发育。这邻苯二甲酸盐暴露与胎盘基因表达之间的联系尚未清除;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确实解决邻苯二甲酸盐暴露和胎龄影响基因在胎盘中表达，但在其他组织中不表达。一个优势之一提出的研究是，我们将无创评估胎盘基因表达通过分泌到细胞外囊泡中的RNA分子孕妇的尿液。收集基因表达数据和化学来自尿液的暴露数据在临床上高度相关，我们希望我们的在家庭怀孕测试时，方法将具有清晰的翻译应用依赖于尿液中胎盘产生的激素的检测已成为常见的。我们提出的研究将为开发用于评估胎盘功能的快速无创测试，化学暴露，并最终在神经发育和其他问题中出现问题怀孕期间的危险信号。