Article

MicroRNAs-Mediators of myometrial contractility during pregnancy and labour

Department of Pediatrics, Children's Medical Center Dallas, 1935 Medical District Drive, Dallas, TX 75235, USA.
Nature Reviews Endocrinology (Impact Factor: 13.28). 05/2013; 9(7). DOI: 10.1038/nrendo.2013.96
Source: PubMed

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.

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    • "Finally, new insights in the epigenetic regulation of chromatin remodeling, gene expression, and long noncoding RNAs (lncRNA) in implantation and decidualization have come to light, such as miRNA regulation of Cox2 (Chakrabarty et al. 2007 ). Furthermore, miRNA regulation of reproductive organs has been implicated in various stages of pregnancy, such as implantation and parturition timing (Liu et al. 2011 ; Renthal et al. 2013 ). DNA methylation in the context of decidual polyploidy has shown to be a requirement in hormone-dependent gene expression, shedding new light on the dynamic gene expression profi les seen in the pregnant uterus under the infl uence of hormones (Gao et al. 2012 ). "
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    ABSTRACT: Embryo implantation is a complex process involving endocrine, para-crine, autocrine, and juxtacrine modulators that span cell–cell and cell–matrix interactions. The quality of implantation is predictive for pregnancy success. Earlier observational studies formed the basis for genetic and molecular approaches that ensued with emerging technological advances. However, the precise sequence and details of the molecular interactions involved have yet to be defi ned. This review refl ects briefl y on aspects of our current understanding of rodent implantation as a tribute to Roger Short's lifelong contributions to the fi eld of reproductive physiology.
    Full-text · Article · Jan 2015 · Advances in anatomy, embryology, and cell biology
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    • "Finally, new insights in the epigenetic regulation of chromatin remodeling, gene expression, and long noncoding RNAs (lncRNA) in implantation and decidualization have come to light, such as miRNA regulation of Cox2 (Chakrabarty et al. 2007 ). Furthermore, miRNA regulation of reproductive organs has been implicated in various stages of pregnancy, such as implantation and parturition timing (Liu et al. 2011 ; Renthal et al. 2013 ). DNA methylation in the context of decidual polyploidy has shown to be a requirement in hormone-dependent gene expression, shedding new light on the dynamic gene expression profi les seen in the pregnant uterus under the infl uence of hormones (Gao et al. 2012 ). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Embryo implantation is a complex process involving endocrine, para-crine, autocrine, and juxtacrine modulators that span cell–cell and cell–matrix interactions. The quality of implantation is predictive for pregnancy success. Earlier observational studies formed the basis for genetic and molecular approaches that ensued with emerging technological advances. However, the precise sequence and details of the molecular interactions involved have yet to be defi ned. This review refl ects briefl y on aspects of our current understanding of rodent implantation as a tribute to Roger Short's lifelong contributions to the fi eld of reproductive physiology.
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