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

pregnancy loss (RPL) is one of the most common abnormalities during pregnancy which,
in its definition should be considered two features: 1- Occurrence of at least
two repeated miscarriages in previous pregnancies 2- These miscarriages occurred
before the 20th week of gestation. The prevalence of RPL in pregnant women is
about 1-5%. Several causes have been reported for this disorder, of which the
most 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 recurrent
pregnancy loss (uRPL). Cell free DNA and RNA in maternal plasma can be
important as non-invasive biomarkers in controlling pregnancy and diagnosing
pregnancy-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 of
inhibiting the expression of genes by two ways: blocking translation and breaking
of mRNA. The miRNAs are derived from a miRNA precursor, which, after processing
through molecule complexes of Dorsha (in nucleus) and Dicer (in cytoplasm), situated
in a RNA-induced silencing complex (RISC). The detection of target mRNAs is carried
out by this complex. Many studies have shown the involvement of miRNAs in
pregnancy and RPL. These can play several roles in this reproductive disorder,
as discussed below: by reducing the expression of genes, miRNAs can cause
abortion, 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 protein
level. Also, in specific populations, some polymorphisms of miRNAs are
differentially expressed, so this can increase the risk of RPL in those
populations. In 2012, a study showed that in patients with spontaneous
abortion, microRNA polymorphisms (miR-146aC> G, miR-149T> C,
miR-196a2T> C and miR-499A> G) are considered as a risk factors of RPL. On
the other hand, circulating miRNAs can serve as a biomarker in the disorder, as
shown in the study by Qin et al., that five miRNAs can be as diagnostic markers
for RPL.  Given the role of these
non-coding RNAs in maternal-fetal angiogenesis, we have investigated the
expression of two miRNAs (miR-16 and miR-21) associated with angiogenesis in
the plasma of patients with uRPL.