Huanhuan Jiang1, Mengting Zhu2, Peipei Guo2, Kaihuan Bi3, Zhimin Lu3, Caihua Li4, Muxin Zhai3, Kangxia Wang5, Yunxia Cao6. 1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. 2. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China. 3. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. 4. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China. 5. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address: 12438410@qq.com. 6. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address: caoyunxia6@126.com.
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.
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.