title: MicroRNAs--mediators of myometrial contractility during pregnancy and labour.
abstract: The maintenance of myometrial quiescence and initiation of contractility, which lead to parturition at term and preterm, involve a shifting equilibrium between anti-inflammatory and proinflammatory signalling pathways. Progesterone (P4), acting through the progesterone receptor (PR), has an essential and multifaceted role in the maintenance of myometrial quiescence. This effect of P4-PR signalling is mediated, in part, by its anti-inflammatory actions and capacity to repress the expression of genes that encode proinflammatory cytokines, such as IL-1 and IL-6, and contraction-associated proteins, such as OXTR, GJA1 and PTGS2. By contrast, increased expression of genes that ultimately lead to parturition is mediated by enhanced inflammatory and estradiol-17β (E2) and estrogen receptor α signalling, which reduce PR function, thus further intensifying the inflammatory response. To obtain a more complete understanding of the molecular events that underlie the transition of the pregnant myometrium from a refractory to a contractile state, the roles of microRNAs, their targets, and their transcriptional and hormonal regulation have been investigated. This article reviews the actions of the miR-200 family and their P4-regulated targets-the transcription factors ZEB1, ZEB2 and STAT5B-in the pregnant myometrium, as well as the role of miR-199a-3p and miR-214 and their mutual target PTGS2. The central role of ZEB1 as the mediator of the opposing actions of P4 and E2 on myometrial contractility will be highlighted.
authors.affiliation: Department of Pediatrics, Children's Medical Center Dallas, 1935 Medical District Drive, Dallas, TX 75235, USA.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Renthal
authors.forename: Koriand'r C
authors.initials: KC
authors.lastname: Williams
authors.forename: Carole R
authors.initials: CR
authors.lastname: Mendelson
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000378:metabolism* / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009215:Myometrium / Q000378:metabolism* / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D011980:Receptors, Progesterone; D011374:Progesterone