The evaluation of CD39, CD73, and HIF-1 α expression besides their related miRNAs in PBMCs of women with recurrent pregnancy loss.

The molecular mechanisms involved in the pathogenesis of recurrent pregnancy loss (RPL) are not completely recognized. The present study aimed to assess the molecules associated with ATP catabolism and hypoxia besides their related miRNAs in patients with RPL. The frequency of Th17 and Treg cells in PBMCs of RPL women and healthy pregnant women were evaluated with Flow cytometry. The expression levels of CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-1α), miR-18a, miR-30a, and miR-206 in PBMCs of two groups were measured with real-time PCR and western blotting. Then, serum levels of IGF-1, TGF-ß, and HIF-1α were measured by ELISA. Our results indicated a higher (p = 0.0002) and lower (p < 0.0001) frequency of Th17 and Treg lymphocytes in RPL women, respectively. The expression level of CD39 decreased in PBMCs of RPL women whereas the level of CD73 and HIF-α increased (p = 0.0010, 0.0023, 0.0006 respectively). The results of CD39 and CD37 were also confirmed by protein analysis (p = 0.0047, 0.0364 respectively). Almost, the same results for CD39 and CD73 expression at mRNA and protein levels were observed in isolated Treg cells. Moreover, we found the higher expression of miR-206 and miRNA-30a (p = 0.0038, 0.0123), but the lower expression of miRNA-18a (p = 0.0101) in RPL. The concentration level of IGF-1, and TGF-ß reduced (p = 0.0017, 0.0065 respectively) while the level of HIF-α elevated (p = 0.0235) in serum samples of RPL. In conclusion, we observed the dysregulation of molecules that are involved in ATP catabolism and hypoxia, including CD39, CD73, and HIF-1a which is related to miR-18a, miR-30a, and miR-206 change in RPL women. It may be potentially used for RPL prognosis by more comprehensive future studies.

Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints.

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre-eclampsia  are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid-derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications.