Abstract
BackgroundStudies have reported that myeloid-derived suppressor cells (MDSCs) contribute to maintain pregnancy. The aim of this case-control study was to test whether there is a dysregulation of peripheral MDSCs in recurrent implantation failure (RIF). Methods26 RIF patients and 30 controls were recruited. Flow cytometry was applied to characterize polymorphonuclear (PMN)-MDSCs, monocytic-MDSCs (M-MDSCs), effector T cells (Teffs) and regulatory T cells (Tregs) in blood. ELISA was used to define MDSCs correlative cytokines and chemokines in serum from all patients. ResultsCompared with controls, RIF patients showed significant reductions of blood PMN-MDSCs, M-MDSCs, Tregs and NO production by PMN-MDSCs, whereas the expression of ζ chain on CD4+T cell receptor (TCR) and CD8+TCR displayed a remarkable upregulation in RIF patients. Moreover, RIF patients presented a lower concentration of serum chemokine (C-C motif) ligand (CCL) 5 and transforming growth factor (TGF)-β than those from controls. Furthermore, the level of TCR ζ chain on CD4+ and CD8+ Teffs was negatively correlated not only with the percentage of PMN-MDSCs, but also with the amount of NO produced by PMN-MDSCs. The frequency of PMN-MDSCs had positive correlations with the concentration of CCL5 and TGF-β. ConclusionsThis study indicated that the dysregulation of MDSCs might impair maternal-fetal immune balance thus resulting in RIF.
Highlights
Recurrent implantation failure (RIF) is diagnosed when women experienced 3 or more frozen or fresh cycles with being transferred high-quality embryos and failed to obtain a clinical pregnancy [1, 2]
Intracellular nitric oxide (NO) production was detected by DAF-2DA utilizing mean fluorescence intensity (MFI)
NO production by PMNMDSCs of recurrent implantation failure (RIF) women was significantly decreased as compared to controls (Fig. 1d, P < 0.01)
Summary
Recurrent implantation failure (RIF) is diagnosed when women experienced 3 or more frozen or fresh cycles with being transferred high-quality embryos and failed to obtain a clinical pregnancy [1, 2]. Lédée et al reports that, at the time of embryo implantation, the maternal immune system is featured by distinct immunological alterations with enrichment of various immune cells in both peripheral circulation and uterus microenvironment [7]. These changes make an immunological tolerance environment which protects embryo expressing paternal antigen from maternal antigen-specific T cells and contributes to successful implantation [7]. Studies have reported that myeloid-derived suppressor cells (MDSCs) contribute to maintain pregnancy The aim of this case-control study was to test whether there is a dysregulation of peripheral MDSCs in recurrent implantation failure (RIF)
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