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A role for micrornas – key regulators of gene expression – in chorioamnionitis and parturition

      Objective

      MicroRNA (miRNA) is a recently discovered RNA family with profound effects on gene expression that result in dramatic phenotypic changes (Nature 2005;438:671). We propose that miRNA plays a role in the control of parturition and inflammation. This study was conducted to determine whether histologic chorioamnionitis and labor at term are associated with changes in miRNA expression in the human chorioamniotic membranes.

      Study design

      Chorioamniotic membranes were obtained from 21 patients in the following groups: 1) normal pregnancy at term in labor; 2) normal pregnancy at term not in labor; 3) spontaneous preterm labor and delivery without histologic chorioamnionitis (PTL); and 4) spontaneous preterm labor and delivery with histologic chorioamnionitis. The relative expression levels of 157 miRNAs were determined by quantitative real-time reverse transcription-polymerase chain reaction. Statistical analysis was performed using generalized estimating equations and the false discovery rate correction.

      Results

      1) Differential regulation of 4 miRNAs was observed in the presence of histologic chorioamnionitis; 2) The expression levels of 5 specific miRNAs decreased with advancing gestational age while 4 specific miRNAs decreased (among PTL); 3) Of major interest, 16 miRNAs were differentially expressed with parturition (see Table). All miRNAs in the Table passed the statistical threshold of p<0.05 after implementation of the false discovery rate correction.
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      Conclusion

      This is the first demonstration of differential expression of miRNA with advancing gestational age, inflammation and spontaneous parturition in the chorioamniotic membranes. The importance of these observations derives from the key role of miRNAs in post-transcriptional regulation of gene expression.