Differential expression of microRNAs with progression of gestation and inflammation in the human chorioamniotic membranes

Abstract

Objective-The aim of this study was to identify differential expression of microRNAs (miRNAs) in chorioamniotic membranes with advancing gestation, labor, and inflammation.Study design-Expression profiles of 157 miRNAs in the chorioamniotic membranes were obtained from patients in the following groups: 1) term not in labor (n=10); 2) term in labor (n=10); 3) preterm labor with histologic chorioamnionitis (n=9); and 4) without histologic chorioamnionitis (n=10).Results-More than 95% of the miRNAs screened were expressed. Gestational age-dependent changes in expression were observed for 13 miRNAs. No differences in miRNA expression were observed between women without labor and women in labor. Membranes with chorioamnionitis displayed increased expression of miR-223 and miR-338. Gene Ontology analysis of genes targeted by differentially expressed miRNAs revealed enrichment for specific biological process categories.Conclusion-Chorioamniotic membranes with advancing gestational age and chorioamnionitis are associated with the differential expression of a subset of miRNAs.

Human amnion mesenchymal cells are pro-inflammatory when activated by the Toll-like receptor 2/6 ligand, macrophage-activating lipoprotein-2

“…Studies have also provided evidence for the potential role of miRNAs in human parturition, as seen by their differential expression patterns in the chorioamnion between preterm and term labor [35] or histologic chorioamnionitis [36]. In this study, miR-320a and miR-18a, had significantly altered expression in AMC after MALP-2 treatment compared to untreated controls (Figure 6B).…”

Exogenous oxytocin modulates human myometrial microRNAs

“…Recent studies have also identified a labor-associated increase of hsa-miR-223-3p in human cervical tissue 8 and in chorioamniotic membranes in the presence of inflammation. 9 Hsa-miR-223-3p has been found to target IKKa during monocyte-macrophage differentiation, which suggests a possible role in the noncanonical and canonical NF-kB pathways, 35 which are important in both term and preterm labor.…”

“…6 A number of recent studies have examined miRNA expression during labor onset in reproductive tissues that have included the placenta, 7 cervix, 8 and fetal membranes. 9 Renthal et al 10 reported that the miR-200 family of miRNAs are upregulated in laboring murine and human myometrium at term. In mouse myometrium, ZEB1 and ZEB2 were identified as 2 targets that act as transcriptional repressors of the contractionassociated genes, which include the oxytocin receptor and connexin-43, through a mechanism that involves the repression of STAT5b, a transcriptional repressor of the P4 metabolizing enzyme 20a-hydroxysteroid dehydrogenase.…”

Maternal inflammation, growth retardation, and preterm birth: Insights into adult cardiovascular disease

“…The daunting numbers of miRs identified at the present time and the multifunctionality of any given miR makes identification of developmentally essential miR activity difficult to discern in such a background. However, a single study found that miR-223 and -338 were dramatically increased in both the mother and the fetus in the context of chorioamnionitis implicating the effects of maternal infection on miR-regulated gene expression (Montenegro et al, 2007).…”