垂体抑制对冻融胚胎不明原因反复胚胎植入失败患者Th17/Treg细胞失衡的影响

Effect of Pituitary Suppression on Th17/Treg Imbalance in Repeated Implantation Failure of Frozen-thawed Embryo

目的:探讨垂体抑制对冻融胚胎不明原因反复胚胎植入失败(uRIF)患者外周血辅助性T细胞17(Th17)和调节性T(Treg)细胞平衡的影响及其降调的可能机制。方法:选择82例35岁以下冻融胚胎uRIF的患者,其中46例单纯激素替代治疗(HRT)为HRT组,36例HRT联合促性腺激素释放激素激动剂(GnRHa)降调为GnRHa降调组,选择正常妊娠早期妇女50例作为对照组。采用流式细胞术(FCM)检测HRT组和GnRHa降调组在HRT备内膜前以及黄体酮转化日外周血中Th17、Treg细胞及Th17/Treg细胞比值,并与对照组比较。结果:与对照组相比,HRT前Th17百分比在GnRHa降调组和HRT组中均升高;Treg细胞百分比均降低,Th17/Treg细胞比值均升高(P<0.05),Th17/Treg细胞平衡向Th17转移。与HRT前相比,黄体酮转化日HRT组和GnRHa降调组Th17百分比降低(P<0.05),Treg细胞百分比升高(P<0.05);黄体酮转化日GnRHa降调组Th17/Treg细胞比值较HRT组明显降低(P<0.05),Th17/Treg细胞平衡向Treg细胞转移。GnRHa降调组雌二醇(E2)水平略高于HRT组,差异无统计学意义(P>0.05)。结论:uRIF患者Th17和Treg细胞数量分别增加和减少,Th17/Treg细胞比值失衡。GnRHa降调可能通过阻断Th17/Treg细胞比值失衡对子宫内膜容受性发挥免疫调节作用,并且这些效应不依赖于外周血中的雌激素水平。

Objective:To investigate the effect of gonadotropin-releasing hormone agonist(GnRHa)on serum Th17/Tregbalance in patients with unexplained repeated implantation failure(uRIF)of froze-thawed embryo and its possible mechanism of downregulation.Methods:Eighty-two patients under 35 years old who had uRIF of frozen-thawed embryoswere enrolled.Forty-six cases received simple hormone replacement therapy(HRT)were defined as HRT group.Another 36 cases received HRT combined with GnRHa downregulation were defined as GnRHa downregulation group.In addition,50 cases of healthy pregnant women in first trimester were selected as control group.The proportion of Th17 cells,Treg cells and Th17/Treg ratio in peripheral blood was detected and compared with control group by Flow cytometry(FCM)before HRT and onthe day of progesterone conversion.Results:Before HRT,the proportion of Th17 increased in GnRHa downregulation group and HRT group compared with that in control group.At the same time,the percentage of Treg cells decreased,the ratio of Th17/Treg cells increased(P<0.05)and the balance of Th17/Treg transferred to Th17 in HRT group compared with the control group.On the day of progesterone conversion,the percentage of Th17 in HRT group and GnRHa downregulation groupdecreased compared with that before HRT(P<0.05),and Treg cells increased(P<0.05).The ratio of Th17/Treg cells decreased significantly in GnRHa downregulation group compared with that in HRT group on the day of progesterone conversion(P<0.05).The balance of Th17/Treg transferred to Treg.The E2 levels of the GnRHa downregulation group were slightly higher than those of the HRT group,with no significant difference between the two groups(P>0.05).Conclusions:There were an increase and a decrease in the number of Th17 and Treg cells,respectively,as well as aTh17/Treg cell imbalanced in unexplained RIF.GnRHa down regulation may play a direct immunomodulatory role in endometrial receptivityby disrupting the imbalance of Th17,Treg cell.These effectsmay be independent of the E2 levels in peripheral blood.