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

• 批准号: 9237148
• 负责人: RUTH A WORD
• 金额: $ 24.3万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9237148
• 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; Gene Targeting; 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; Pregnancy; Premature Birth; Premature Labor; Progesterone; Progesterone Receptors; Property; Prostaglandins; Proteins; RNA; RNA Polymerase II; Receptor Activation; Refractory; Regulation; Research; Role; Signal Pathway; Signal Transduction; Stromal Cells; 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; pregnant; premature; progesterone receptor A; progesterone receptor B; programs; receptor function; reproductive; transcription factor; transcriptome; treatment response

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.

摘要 预测早产最有效的单一指标是宫颈状况。 早产的症状。足月生理性宫颈成熟的机制 在很大程度上是未知的，早产宫颈扩张的原因更是难以捉摸。我们的 实验室，加上基因组和分子分析方面的互补专业知识，已经 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 深入研究分子转录和基因组的更完整的方法 足月正常分娩的生理学基础及其病理生理学机制 早产。在这里，我们建议：(I)确定雌激素受体拮抗剂是否阻断早产宫颈 成熟和分娩，(Ii)探索PR和ER介导的信号通路的全球效应 人宫颈上皮和间质细胞及其抑制PR的细胞机制 内质网介导的信号转导，以及(Iii)确定内质网介导的信号通路在 活体宫颈成熟和扩张。