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

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.

[1]  Yu Cao,et al.  Sildenafil might impair maternal-fetal immunotolerance by suppressing myeloid-derived suppressor cells in mice. , 2020, Journal of reproductive immunology.

[2]  G. Song,et al.  Function of CCL5 in maternal-fetal interface of pig during early pregnancy. , 2020, Developmental and comparative immunology.

[3]  C. Chiang,et al.  Distinct Role of CD11b+Ly6G−Ly6C− Myeloid-Derived Cells on the Progression of the Primary Tumor and Therapy-Associated Recurrent Brain Tumor , 2019, Cells.

[4]  M. Garstka,et al.  Chemokines and their receptors promoting the recruitment of myeloid-derived suppressor cells into the tumor. , 2019, Molecular immunology.

[5]  A. Kotsakis,et al.  Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer , 2019, Cells.

[6]  H. Kurahashi,et al.  Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. , 2019, Human reproduction.

[7]  Marie-Pierre L. Gauthier,et al.  Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis , 2019, Critical Care.

[8]  A. Zenclussen,et al.  Human Miscarriage Is Associated With Dysregulations in Peripheral Blood-Derived Myeloid Dendritic Cell Subsets , 2019, Front. Immunol..

[9]  M. Yousefi,et al.  Oxidative stress, inflammatory settings, and microRNA regulation in the recurrent implantation failure patients with metabolic syndrome , 2019, American journal of reproductive immunology.

[10]  P. Laissue,et al.  FOXD1 mutations are related to repeated implantation failure, intra-uterine growth restriction and preeclampsia , 2019, Molecular Medicine.

[11]  H. Yi,et al.  Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome , 2019, Front. Endocrinol..

[12]  M. Huber-Lang,et al.  Immunostimulatory functions of adoptively transferred MDSCs in experimental blunt chest trauma , 2019, Scientific Reports.

[13]  N. Kim,et al.  Genetic polymorphisms of the cobalamin transport system are associated with idiopathic recurrent implantation failure , 2019, Journal of Assisted Reproduction and Genetics.

[14]  Yan Zhang,et al.  Myeloid‐derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells , 2019, American journal of reproductive immunology.

[15]  P. Arck,et al.  Impaired Progesterone-Responsiveness of CD11c+ Dendritic Cells Affects the Generation of CD4+ Regulatory T Cells and Is Associated With Intrauterine Growth Restriction in Mice , 2019, Front. Endocrinol..

[16]  A. Decherney,et al.  Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model , 2019, Reproductive Sciences.

[17]  C. Poets,et al.  HIF-1α-Deficiency in Myeloid Cells Leads to a Disturbed Accumulation of Myeloid Derived Suppressor Cells (MDSC) During Pregnancy and to an Increased Abortion Rate in Mice , 2019, Front. Immunol..

[18]  Kiran Singh,et al.  Altered crosstalk of estradiol and progesterone with Myeloid‐derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal‐fetal tolerance , 2019, American journal of reproductive immunology.

[19]  Xiaorui Liu,et al.  Differential gene expression profile in monocytic myeloid‐derived suppressor cells at maternal–fetal interface in a mouse model of spontaneous abortion , 2018, Journal of cellular physiology.

[20]  P. Descamps,et al.  Surgical treatment of septate uterus in cases of primary infertility and before assisted reproductive technologies. , 2018, Journal of gynecology obstetrics and human reproduction.

[21]  Alison S Care,et al.  Regulatory T cells in embryo implantation and the immune response to pregnancy , 2018, The Journal of clinical investigation.

[22]  C. Poets,et al.  Granulocytic myeloid‐derived suppressor cells (GR‐MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period , 2018, Clinical and experimental immunology.

[23]  Y. Shaked,et al.  CCR5 Directs the Mobilization of CD11b+Gr1+Ly6Clow Polymorphonuclear Myeloid Cells from the Bone Marrow to the Blood to Support Tumor Development. , 2017, Cell reports.

[24]  N. Macklon.  Recurrent implantation failure is a pathology with a specific transcriptomic signature. , 2017, Fertility and sterility.

[25]  Xiangshan Fan,et al.  Abnormal ratio of CD57+ cells to CD56+ cells in women with recurrent implantation failure , 2017, American journal of reproductive immunology.

[26]  A. Enk,et al.  Tadalafil has biologic activity in human melanoma. Results of a pilot trial with Tadalafil in patients with metastatic Melanoma (TaMe) , 2017, Oncoimmunology.

[27]  P. Sinha,et al.  Frontline Science: Myeloid‐derived suppressor cells (MDSCs) facilitate maternal–fetal tolerance in mice , 2017, Journal of leukocyte biology.

[28]  T. Pan,et al.  Myeloid‐derived suppressor cells are essential for maintaining feto‐maternal immunotolerance via STAT3 signaling in mice , 2016, Journal of leukocyte biology.

[29]  Canquan Zhou,et al.  Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF-ICSI cycles. , 2016, Reproductive biomedicine online.

[30]  Peter J. Murray,et al.  Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards , 2016, Nature Communications.

[31]  A. Zhao,et al.  Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4+CD25-T cells by activation of the TGF-β/β-catenin pathway. , 2016, Molecular human reproduction.

[32]  S. Häusler,et al.  CD33+/HLA‐DRneg and CD33+/HLA‐DR+/− Cells: Rare Populations in the Human Decidua with Characteristics of MDSC , 2016, American journal of reproductive immunology.

[33]  G. Chaouat,et al.  The Uterine Immune Profile May Help Women With Repeated Unexplained Embryo Implantation Failure After In Vitro Fertilization , 2016, American journal of reproductive immunology.

[34]  Chunyu Huang,et al.  The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure. , 2015, Reproductive biomedicine online.

[35]  Kiran Singh,et al.  Reduced Myeloid‐derived Suppressor Cells in the Blood and Endometrium is Associated with Early Miscarriage , 2015, American journal of reproductive immunology.

[36]  D. Stevenson,et al.  Unique Roles of Infiltrating Myeloid Cells in the Murine Uterus during Early to Midpregnancy , 2015, The Journal of Immunology.

[37]  C. Poets,et al.  Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T‐cell responses , 2014, European journal of immunology.

[38]  H. Jaspan,et al.  The Role of Myeloid-Derived Suppressor Cells in Immune Ontogeny , 2014, Front. Immunol..

[39]  S. Sunkara,et al.  Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. , 2014, Human reproduction update.

[40]  Yang Zhang,et al.  Quantitative Reduction of Peripheral CD4+CD25+FOXP3+ Regulatory T cells in Reproductive Failure after Artificial Insemination by Donor Sperm , 2013, American journal of reproductive immunology.

[41]  A. Erlebacher.  Mechanisms of T cell tolerance towards the allogeneic fetus , 2012, Nature Reviews Immunology.

[42]  Haixiang Sun,et al.  An Increase of Treg Cells in the Peripheral Blood is Associated with a Better In Vitro Fertilization Treatment Outcome , 2012, American journal of reproductive immunology.