Differentially expressed circulating microRNAs associated with idiopathic recurrent pregnancy loss.

Abstract

Recurrent pregnancy loss (RPL) is a major pregnancy complication which reportedly affects 2-3% of all pregnancies. Currently, RPL lacks an effective therapy and a reliable diagnostic and prognostic biomarker. Circulating microRNAs were recently described as potential biomarkers of pregnancy-associated complications. The aim of this study was to determine microRNA expression patterns in the plasma of RPL patients as potential early biomarker of RPL. Study subjects comprised 20 women with early RPL (miscarriage at 8-12weeks of gestation), and 20 age- and gestation-matched multiparous control women. Circulating microRNAs were extracted from maternal plasma, and the differential microRNA expression were determined using customized pathway-focused miRNA profiler kit. Of the 10 differentially-expressed microRNAs identified, Hsa-let-7e, Hsa-miR-221-3p, Hsa-miR-16, Hsa-miR-519d, Hsa-miR-184, Hsa-miR-410 were upregulated, while Hsa-miR-21, Hsa-miR-125, Hsa-let-7a, Hsa-let-7d were downregulated in RPL cases as compared to control women. Of these, 5 novel microRNAs were reported for the first time to be associated with RPL. These comprised Hsa-let-7e, Hsa-miR-519d, Hsa-miR-410 which were upregulated, and Hsa-let-7a, Hsa-let-7d which were downregulated in RPL. While its association with RPL was reported earlier, this study is also the first to report on the upregulation of Hsa-miR-184 in circulating fluids in association with RPL. The study provides for understanding circulating microRNAs expression pattern in RPL which may be involved in its pathogenesis and demonstrates their potential role as noninvasive diagnostic and prognostic biomarkers for RPL.