Hence,we examined the expression of miR-16 and VEGF-A in both plasma and PBMCs and foundthat although higher expression level of miR-16 in the plasma of uRM group comparedwith the control group, it was not significant but in PBMCs, its expressionlevel was statistically significant.

Also, in these cells, expression level of VEGF-Ain the uRM group was more than P <.05. Thus, it can be concluded that thereis no significant relationship between miR-16 and VEGF-A in mRNA levels. This resultwas incompatible with the study of Amirchaghmaghi et al, which was carried outat the protein level.

(22). It ispossible that this relationship exists only at the levels of protein expression.Inanother investigation, we studied the expression of miR-21 and PTEN in PBMCs andshowed that there is a relation between their expression levels, so that miR-21and PTEN in women with uRM was downregulated and upregulated, respectively.

Thesefindings were consistent with the study by Tokyol et al in 2008, that showed a remarkableincrease in the expression of PTEN in decidua and trophoblast cells of patientswith RM (23). Also, plasmaanalysis of these patients revealed a decrease in miR-21 expression, which was similarto the findings of El-Shorafa et al (24). Consideringthat investigations has shown that embryo development is associated withsimilar mechanisms with tumor invasion (16), there is apossibility for involvement  of thesegenes in maternal angiogenesis. In 2011, a study conducted to examine theeffect of miR-21 on human tumor cells demonstrated that with increasing theexpression of this miRNA, Akt/Erk signaling pathways are activated, that leadingto increased expression of HIF-1? and VEGF, and  also enhances angiogenesis (20). In recurrent miscarriage,the angiogenesis can occur inversely, which means that by reducing theangiogenesis, nutrient delivery to the fetus is reduced and miscarriage may takesplace. Althoughin our study, the VEGF-A expression was not significantly altered, but inaccordance with studies performed (22, 25), it is likelythat its expression at the protein level will be significant.

Therefore,further research is needed in this regard and our proposed model in associatedwith this study is as follows:

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