甲状腺自身抗体阳性患者外周血中CD4^+T细胞特异性转录因子的表达及其对IVF-ET治疗结局的影响

The expression of CD4^+T cells relative characteristic transcription factors in patients with ATA+and its influence on in vitro fertilization and embryo transfer pregnancy outcomes

目的:探究甲状腺功能正常甲状腺自身抗体阳性患者外周血中CD4^+T细胞特异性转录因子(T-bet mRNA、GATA-3 mRNA、RORγt mRNA和FoxP3 mRNA)表达量及其对体外受精-胚胎移植(IVF-ET)治疗结局的影响。方法:选取在青岛大学附属烟台毓璜顶医院生殖医学科接受IVF治疗的甲状腺功能正常的患者,其中行新鲜周期胚胎移植且甲状腺自身抗体阳性(ATA^+)患者28例,甲状腺自身抗体阴性(ATA^-)患者32例。取卵日、移植第5天、移植第14天抽取患者外周血,逆转录多聚酶链反应(RT-qPCR)检测4种转录因子。结果:ATA^+组的生化妊娠流产率明显高于ATA^-组(P<0.05)。ATA^+组的着床率、囊胚率、临床妊娠率和活产率与ATA^-组比较有降低趋势,早期流产率与ATA^-组比较有升高趋势(P>0.05)。ATA^+组取卵日外周血T-bet mRNA表达量明显高于ATA^-组,移植第14天外周血中GATA-3 mRNA表达量明显低于ATA^-组,取卵日、移植第5天、移植第14天外周血中RORγt mRNA表达量显著高于ATA^-组;而FoxP3 mRNA表达量显著低于ATA^-组(P<0.05)。取卵日、移植第5天、移植第14天ATA^+组外周血中T-bet mRNA/GATA-3 mRNA和RORγt mRNA/FoxP3 mRNA比值均显著高于ATA^-组(P<0.05)。结论:ATA^+患者外周血中T-bet mRNA/GATA-3 mRNA和RORγt mRNA/FoxP3 mRNA比值在取卵日、移植第5天、移植第14天外周血中均明显增高,导致外周血中CD4^+T细胞之间的平衡被打破,可能是ATA^+患者导致IVF-ET治疗不良妊娠结局的免疫学机制之一。

Objective:To study the expression of CD4^+T cells related characteristic transcription factors(T-bet mRNA,GATA-3 mRNA,RORγt mRNA,and FoxP3 mRNA) in peripheral blood of patients with normal thyroid function while positive anti-thyroid autoantibody and its influence on IVF-ET pregnancy outcomes.Method:A prospective study of patients with normal thyroid function who received IVF-ET treatment in Department of Reproductive Medicine of Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University,among the patients,28 received fresh cycle embryo transfer with positive anti-thyroid autoantibodies(ATA^+),and 32 patients with negative anti-thyroid autoantibodies(ATA^-).Blood samples of two groups of patients were collected on oocyte retrieval days,the 5 th day after transplantation,and the 14 th day after transplantation were tested through RT-qPCR for four transcription factors.Result:The biochemical pregnancy abortion rate in ATA^+ group was significantly higher than that in ATA^- group(P<0.05).The implantation rate,blastocyst rate,clinical pregnancy rate and live birth rate in ATA^+ group were lower than those in ATA^- group,and the early abortion rate was higher than that in ATA^- group(P>0.05).The expression level of T-bet mRNA in peripheral blood of ATA^+ group was significantly higher than ATA^- group on oocyte retrieval days.The expression level of GATA-3 mRNA in peripheral blood of ATA^+ group was significantly lower than ATA^- group on the 14 th day after transplantation.The expression level of RORγt mRNA in peripheral blood of ATA^+ group was significantly higher than ATA^- group on oocyte retrieval days,the 5 th day and the 14 th day after transplantation.The expression level of FoxP3 mRNA in peripheral blood of ATA^+ group was significantly lower than ATA^- group on oocyte retrieval days,the 5 th day and the 14 th day after transplantation(P<0.05).The ratio of T-bet mRNA/GATA-3 mRNA and RORγt mRNA/FoxP3 mRNA in peripheral blood drawn on oocyte retrieval days,the 5 th day and the 14 th day after transplantation of ATA^+ group was significantly higher than in ATA^- group(P<0.05).Conclusion:The ratio of T-bet mRNA/GATA-3 mRNA and RORγt mRNA/FoxP3 mRNA in peripheral blood of ATA^+ patients increased significantly on oocyte retrieval days,the 5 th day and the 14 th day after transplantation,resulting in the imbalance of CD4^+T cells in peripheral blood,which may be one of the immunological mechanisms of ATA^+ patients leading to adverse pregnancy outcomes in IVF treatment.