Recurrent miR-196a2T> C and miR-499A> G) are considered as

Recurrentpregnancy loss (RPL) is one of the most common abnormalities during pregnancy which,in its definition should be considered two features: 1- Occurrence of at leasttwo repeated miscarriages in previous pregnancies 2- These miscarriages occurredbefore the 20th week of gestation. The prevalence of RPL in pregnant women isabout 1-5%.

Several causes have been reported for this disorder, of which themost important are: Genetic anomalies, immune and biochemical disorders,thrombophilia, infections, uterine anatomical disorders, and lifestyle. However,more than 50% of cases, the causes remain unknown, which is called unexplained recurrentpregnancy loss (uRPL). Cell free DNA and RNA in maternal plasma can beimportant as non-invasive biomarkers in controlling pregnancy and diagnosingpregnancy-related disorders and one of these RNAs is non-coding RNAs. MicroRNAs(miRNAs), as a type of small non-coding RNAs, are involved in the process ofinhibiting the expression of genes by two ways: blocking translation and breakingof mRNA.

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The miRNAs are derived from a miRNA precursor, which, after processingthrough molecule complexes of Dorsha (in nucleus) and Dicer (in cytoplasm), situatedin a RNA-induced silencing complex (RISC). The detection of target mRNAs is carriedout by this complex. Many studies have shown the involvement of miRNAs inpregnancy and RPL. These can play several roles in this reproductive disorder,as discussed below: by reducing the expression of genes, miRNAs can causeabortion, for example, by reducing the expression of genes, miRNAs can cause miscarriage.For example, miR-133a is upregulated in patients with recurrent miscarriage,and can lead to abortion through decreasing the HLA-G expression at the proteinlevel. Also, in specific populations, some polymorphisms of miRNAs aredifferentially expressed, so this can increase the risk of RPL in thosepopulations. In 2012, a study showed that in patients with spontaneousabortion, microRNA polymorphisms (miR-146aC> G, miR-149T> C,miR-196a2T> C and miR-499A> G) are considered as a risk factors of RPL.

Onthe other hand, circulating miRNAs can serve as a biomarker in the disorder, asshown in the study by Qin et al., that five miRNAs can be as diagnostic markersfor RPL.  Given the role of thesenon-coding RNAs in maternal-fetal angiogenesis, we have investigated theexpression of two miRNAs (miR-16 and miR-21) associated with angiogenesis inthe plasma of patients with uRPL.