http://dx.doi.org/10.5455/2320-1770.ijrcog20130914 Volume 2 · Issue 3 Page 330 International Journal of Reproduction, Contraception, Obstetrics and Gynecology El-Shorafa HM et al. Int J Reprod Contracept Obstet Gynecol. 2013 Sep;2(3):330-335 www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789 Research Article Dysregulation of micro-RNA contributes to the risk of unexplained recurrent pregnancy loss Heba M. El-Shorafa, Fadel A. Sharif* INTRODUCTION Micro-RNAs are small, evolutionarily conserved, single stranded, non-coding RNA molecules that bind target mRNA to prevent protein production by one of two distinct mechanisms: translation inhibition or degradation of mRNA. Mature miRNA is generated through two-step cleavage of a precursor miRNA (pre-miRNA), where RNA-induced silencing complex (RISC) is involved in the process (Hutzinger and Izaurralde, 2011). The miRNA functions as a guide by base-pairing with target mRNA to negatively regulate its expression. The level of complementarity between the guide and mRNA target determines which silencing mechanism will be employed; cleavage of target mRNA with subsequent degradation or translation inhibition (Hutzinger and Izaurralde, 2011). Earlier studies have revealed that miRNAs have key roles in diverse regulatory pathways, including control of developmental timing, hematopoietic cell differentiation, apoptosis, cell proliferation and organ development (Kim, 2005). miRNAs have also been implicated in various multifactorial human diseases such as cancers (Calin and Croce, 2006), cardiovascular disease (Thum et al, 2008), Department of Medical Laboratory Sciences, Islamic University of Gaza, Gaza, Palestine Received: 27 May 2013 Accepted: 15 June 2013 *Correspondence: Dr. Fadel A. Sharif E-mail: fsharif@iugaza.edu.ps © 2013 El-Shorafa HM et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Although there are plenty of evidence that dysregulation of microRNA (miRNA) level is involved in many human diseases, it is still unknown whether abnormal levels of specific miRNAs are associated with recurrent pregnancy loss (RPL). We believe that such an association do exist as this study confirmed significant differences in the level of specific miRNAs between RPL cases and healthy controls. The study was conducted on 100 Palestinian women: 60 patients with at least two unexplained consecutive pregnancy losses half of them were pregnant at the first trimester and the rest were non-pregnant and 40 healthy controls with at least two live births and no history of pregnancy loss; half of them were at their first trimester of pregnancy and the rest were non-pregnant. We investigated the relative expression of miR-21, miR-126, miR-155, miR-182, miR-222 and miR-517* using quantitative real-time polymerase chain reaction and Ct method experiments. Differential expression was evaluated using Student t-test and fold change analyses. The expression difference of miR-21, miR-126 and miR-182 between patients and controls in the pregnant subjects showed statistically significant difference (p-value ≤ 0.05) with fold decrease of 1.5, 1.6 and 5.6, respectively. In the non-pregnant group miR-21, miR-126, miR-222 and miR-517* expressions were significantly different with fold decrease of 2.4, 2.9, 2.7 and 11.8, respectively. In conclusion, at least miR-21 and miR-126 could serve as potential markers for idiopathic RPL as their levels were significantly lower in patients before being pregnant and during pregnancy. Moreover, restoration of the normal level of those miRNAs might be a novel intervention strategy in unexplained RPL. Keywords: miRNAs, Recurrent pregnancy loss DOI: 10.5455/2320-1770.ijrcog20130914