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Genomic Consequences of Estrogen Receptor Activation in the Cervix

子宫颈雌激素受体激活的基因组后果

基本信息

批准号：
10204064
负责人：
MALA S. MAHENDROO
金额：
$ 23.81万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10204064
关键词：
Address Agonist Animal Model Animals Binding Binding Sites Bioinformatics Biological Sciences Biology Biomechanics Birth Cavia Cell model Cells Cervical Cervical Ripening Cervix Uteri Coculture Techniques Competence Data EP300 gene Enhancers Epithelial Cells Estradiol Estrogen Receptor alpha Estrogen Receptor beta Estrogen Receptors Estrogens Event Extracellular Matrix Functional disorder Gene Expression Gene Proteins Genes Genetic Transcription Genomics Goals Hormones Human Immune Induced Labor Infant Mortality Infiltration Inflammatory Response Pathway Laboratories Length MMP11 gene Maintenance Mediating Methodology Mifepristone Modeling Molecular Molecular Analysis Nuclear Outcome Oxytocin Pathway interactions Peptide Hydrolases Physiological Physiology Play Polymerase Pregnancy Premature Birth Premature Labor Progesterone Progesterone Receptors Property Prostaglandins Proteins RNA Receptor Activation Refractory Regulation Research Role Signal Pathway Signal Transduction Stromal Cells Structure Symptoms Testing Tissues Vagina Withdrawal Work chemokine chromatin immunoprecipitation deep sequencing experience global run on sequencing histone modification in vivo myometrium next generation sequencing novel porcine model pregnant premature progesterone receptor A progesterone receptor B programs receptor function reproductive transcription factor transcriptome transcriptome sequencing treatment response

项目摘要

ABSTRACT The single most effective predictor of preterm birth is the state of cervix upon presentation with symptoms of preterm labor. The mechanisms underlying physiological cervical ripening at term are largely unknown, and the causes of preterm cervical dilation are even more elusive. Our laboratory, together with complementary expertise in genomic and molecular analysis, has expanded its long-term strength in the biology and physiology of human parturition to include a more integrated approach to delve deeply into the molecular transcriptional and genomic mechanisms that underpin the physiology of normal labor at term and the pathophysiology of preterm birth. Here, we propose (i) to determine if ER antagonists block preterm cervical ripening and labor, (ii) to explore the global effects of PR- and ER-mediated signaling pathways in human cervical epithelial and stromal cells and the cellular mechanisms by which PRs inhibit ER-mediated signaling, and (iii) to determine the role of ER-mediated signaling pathways in cervical ripening and dilation in vivo.

抽象的早产的唯一最有效的预测因素是出现时的子宫颈状态早产的症状。足月生理性宫颈成熟的机制目前尚不清楚，早产宫颈扩张的原因更是难以捉摸。我们的实验室以及基因组和分子分析方面的互补专业知识，扩大了其在人类分娩生物学和生理学方面的长期实力，包括更综合的方法来深入研究分子转录和基因组支持正常足月分娩的生理学机制和病理生理学早产。在这里，我们建议 (i) 确定 ER 拮抗剂是否可以阻断早产宫颈癌成熟和分娩，(ii) 探索 PR 和 ER 介导的信号通路的整体影响在人宫颈上皮细胞和基质细胞中的作用以及 PR 抑制的细胞机制 ER 介导的信号传导，以及 (iii) 确定 ER 介导的信号传导途径在体内宫颈成熟和扩张。