Genomic Consequences of Estrogen Receptor Activation in the Cervix

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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 from other projects in this application, 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 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.