Th1/Th2细胞平衡及NK细胞对胚胎种植的影响

Effect of Th1/Th2 balance and NK cells on embryo implantation

目的:通过研究反复种植失败(RIF)患者与首次移植妊娠成功患者种植窗口期外周血中Th1、Th2型细胞因子及自然杀伤(NK)细胞的表达差异,探讨Th1/Th2细胞平衡及NK细胞对胚胎种植的影响及调节机制。方法:选取2020年3月至2020年9月于山东大学齐鲁医院不孕不育诊疗中心就诊的35例RIF患者(RIF组)和首次行体外受精(IVF)或卵细胞浆内单精子注射(ICSI)助孕即成功妊娠的29例不孕症患者(对照组)。于胚胎移植治疗前的黄体中期采集患者外周血,流式细胞术检测Th1型细胞因子IL-2、IFN-γ、TNF-α,Th2型细胞因子IL-4、IL-6、IL-10以及NK细胞水平。结果:种植窗口期RIF组患者外周血中IL-6及IL-2/IL-10、IFN-γ/IL-10和TNF-α/IL-10比值明显高于对照组,IL-10水平明显低于对照组,差异有统计学意义(P<0.05)。RIF组患者外周血中IL-2、IL-4水平及TNF-γ含量高于对照组,TNF-α含量低于对照组,但差异无统计学意义(P>0.05)。两组患者血清中NK细胞比例无明显统计学差异(P>0.05)。结论:IL-6、IL-10可能参与种植窗口期外周血中Th1/Th2细胞平衡调节,从而影响胚胎的种植。

Objective:To explore the effect and mechanism of Th1/Th2 balance and NK cells on embryo implantation by investigating the expression of Th1/Th2-type cytokines and NK cells in peripheral blood of patients with repeated implantation failure(RIF),compared to controls with a successful pregnancy in the first in vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET)cycle.Methods:From March 2020 to September 2020,35 cases with RIF were collected from the Infertility Center of Qilu Hospital of Shandong University as RIF group,29 cases with a successful pregnancy in the first IVF/ICSI-ET cycle were collected as the control group.Th1-type cytokines(IL-2,IFN-γ,TNF-α),Th2-type cytokines(IL-4,IL-6,IL-10)and NK cells were detected by flow cytometry.All blood samples were drawn in the mid-luteal phase prior to IVF/ICSI-ET treatment.Results:The IL-6 concentration was higher,the IL-10 concentration was lower in the RIF group than that in the control group.The ratios of IL-2/IL-10,IFN-γ/IL-10 and TNF-α/IL-10 were higher in the RIF group than that in the control group(P<0.05).The IL-2,IL-4 and IFN-γconcentrations were higher,while the TNF-αconcentration was lower in the RIF group than that in the control group,but the difference was not statistically significant(P>0.05).There was no significant difference in NK cells between the two groups(P>0.05).Conclusion:IL-6 and IL-10 may be involved in the Th1/Th2 balance in peripheral blood during the implantation window,thereby affecting embryo implantation.