Gong Qiaoqiao, Zhu Yuejie, Pang Nannan, Ai Haiquan, Gong Xiaoyun, La Xiaolin, Ding Jianbing
Reproductive Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
Department of Immunology, School of Preclinical Medicine, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Exp Ther Med. 2017 Dec;14(6):5931-5941. doi: 10.3892/etm.2017.5334. Epub 2017 Oct 18.
fertilization-embryo transfer (IVF-ET) can be used by infertile couples to assist with reproduction; however, failure of the embryo to implant into the endometrial lining results in failure of the IVF treatment. The present study investigated the expression of chemokine receptor 7 (CCR7)(lo) programmed death-1(PD-1)(hi) chemokine receptor type 5 (CXCR5) cluster of differentiation 4 (CD4) T cells and associated factors in patients with repeated implantation failure (RIF). A total of 30 females with RIF and 30 healthy females were enrolled in the current study. Flow cytometry was used to detect the proportion of CCR7(lo)PD-1(hi) CXCR5 CD4 T cells in the peripheral blood. Cytokine bead arrays were performed to detect the levels of interleukin (IL)-6, -4 and -2 in the serum. ELISAs were used to detect the level of IL-21 in the serum. Quantitative real time polymerase chain reaction analysis and immunohistochemistry were used to investigate the expression of B-cell lymphoma 6 (Bcl-6), chemokine receptor type 5 (CXCR5) and IL-21 in the endometrium. The results revealed that the percentage of CCR7(lo)PD-1(hi) CXCR5 CD4 T cells was increased in the RIF group compared with the control group during the mid luteal phase. The mRNA and protein levels of Bcl-6, IL-21 and CXCR5 in the endometrium and the concentrations of IL-21 and IL-6 in the serum were significantly increased in the RIF group; however, no significant difference was observed between the two groups in regards to the expression of IL-4 and IL-2. Furthermore, a significant positive correlation was identified between the percentage of CCR7(lo)PD-1(hi) CXCR5 CD4 T cells and IL-21 and IL-6 levels. The expression of IL-21 also had a positive correlation with Bcl-6 and CXCR5 expression in the RIF group. These results suggest that increased levels of CCR7(lo)PD-1(hi) CXCR5 CD4 T cells and associated factors contribute to RIF and could therefore be a potential therapeutic target.
体外受精 - 胚胎移植（IVF - ET）可被不孕夫妇用于辅助生殖；然而，胚胎未能植入子宫内膜会导致IVF治疗失败。本研究调查了反复种植失败（RIF）患者中趋化因子受体7（CCR7）低表达、程序性死亡 - 1（PD - 1）高表达、趋化因子受体5（CXCR5）、分化簇4（CD4）T细胞及相关因子的表达情况。本研究共纳入30例RIF女性患者和30例健康女性。采用流式细胞术检测外周血中CCR7低表达、PD - 1高表达、CXCR5 CD4 T细胞的比例。进行细胞因子微珠阵列检测血清中白细胞介素（IL）-6、-4和 -2的水平。采用酶联免疫吸附测定（ELISA）检测血清中IL -21的水平。运用定量实时聚合酶链反应分析和免疫组织化学法研究子宫内膜中B细胞淋巴瘤6（Bcl -6）、趋化因子受体5（CXCR5）和IL -21的表达。结果显示，在黄体中期，RIF组CCR7低表达、PD - 1高表达、CXCR5 CD4 T细胞的百分比高于对照组。RIF组子宫内膜中Bcl -6、IL -21和CXCR5的mRNA及蛋白水平以及血清中IL -21和IL -6的浓度显著升高；然而，两组在IL -4和IL -2的表达方面未观察到显著差异。此外，CCR7低表达、PD - 1高表达、CXCR5 CD4 T细胞的百分比与IL -21和IL -6水平之间存在显著正相关。在RIF组中，IL -21的表达与Bcl -6和CXCR5的表达也呈正相关。这些结果表明，CCR7低表达、PD - 1高表达、CXCR5 CD4 T细胞及相关因子水平的升高导致了RIF，因此可能是一个潜在的治疗靶点。
