Increased Uterine NK cell numbers and perforin expression during the implantation phase in IVF Cycles with GnRH Antagonist Protocol.

Increased Uterine NK cell numbers and perforin expression during the implantation phase in IVF Cycles with GnRH Antagonist Protocol.
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使用 GnRH 拮抗剂方案在 IVF 周期植入阶段增加子宫 NK 细胞数量和穿孔素表达

DOI:
10.1038/srep39912
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发表时间:
2017-01-03
期刊:
影响因子:
4.6
通讯作者:
Zhang A
Zhang A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu B;Wang J;Xia L;Zhang D;Wu X;Zhang A

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GnRH拮抗剂在体外受精(IVF)周期中对子宫内膜容受性产生负面影响,但其潜在机制尚不清楚。为了探索其靶分子,我们研究了固定GnRH拮抗剂、低剂量柔性GnRH拮抗剂、GnRH激动剂长期方案和未治疗对照组的窗口期子宫内膜。与对照组相比,固定拮抗剂组有384个差异表达基因(DEGs)的表达变化大于2倍,固定拮抗剂组与激动剂组之间有197个差异表达基因(DEGs),其中大部分与自然杀伤(NK)细胞介导的细胞毒性途径相关。然后我们分析了PRF1和FASLG蛋白水平。两种拮抗剂组的穿孔素水平均显著高于其他两组,固定拮抗剂组的穿孔素水平更高。同样,拮抗剂组的uNK细胞数也较高,其中固定组的uNK细胞数最高(p < 0.05)。3个治疗组间Fas配体水平和凋亡率无显著差异,但治疗组高于对照组。总之,这些数据表明GnRH拮抗剂可能增加uNK细胞数量和穿孔素表达,并且这种作用可能是剂量依赖性的。
GnRH antagonist negatively affects endometrial receptivity inin vitrofertilization (IVF) cycles, however, its underlying mechanism remains unclear. To explore its target molecules, we studied endometria in the window phase of fixed GnRH antagonist, low-dose flexible GnRH antagonist, GnRH agonist long protocol, and untreated control groups. There were 384 differentially expressed genes (DEGs) in the fixed antagonist group with greater than twofold expression change compared with the control group and 197 DEGs between the fixed antagonist and agonist groups, the majority of which were associated with the natural killer (NK) cell-mediated cytotoxicity pathway. We then analysed the PRF1 and FASLG protein levels. The perforin level were significantly higher in both the antagonist groups than in other two groups, and was higher in the fixed antagonist group. Similarly, the uNK cell numbers were higher in the antagonist groups, and the highest uNK cell number occurred in the fixed group (p < 0.05). No significant differences existed in the Fas ligand levels and apoptosis rates among the three treatment groups, but were higher in the treatment groups than the control group. Together, these data indicate that GnRH antagonist may increase the uNK cell numbers and perforin expression, and this effect may be dose-dependent.
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