Impaired myeloid-derived suppressor cells are associated with recurrent implantation failure: A case-control study

Abstract

Background: 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).

Methods: 26 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.

Results: Compared 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.

Conclusions: This study indicated that the dysregulation of MDSCs might impair maternal-fetal immune balance thus resulting in RIF.

Keywords: Maternal-fetal immune tolerance; Myeloid-derived suppressor cells; Recurrent implantation failure; Regulatory T cells.