GnRH antagonist alters the migration of endometrial epithelial cells by reducing CKB
GnRH antagonist alters the migration of endometrial epithelial cells by reducing CKB
复制标题
GnRH 拮抗剂通过减少 CKB 改变子宫内膜上皮细胞的迁移
DOI：
10.1530/rep-19-0578
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发表时间：
2020-06-01
期刊：
影响因子：
3.8
通讯作者：
Xu, Chen
中科院分区：
文献类型：
--
作者：
Chen, Qian;Fan, Yong;Xu, Chen
一些研究表明，在体外受精（IVF）过程中，促性腺激素释放激素拮抗剂（GnRH-ant）方案的新鲜移植周期着床率低于GnRH激动剂（GnRH-a）方案。这种效应可能与子宫内膜容受性有关。然而，其机制尚不清楚。本研究评估了接受GnRH-a或GnRH-ant方案治疗的中期分泌期患者和处于自然周期的患者的子宫内膜组织。在着床期起重要作用的b型肌酸激酶（CKB）在GnRH-ant组的子宫内膜表达显著降低。同时，GnRH-ant组子宫内膜容受性标志物HOXA10的表达明显降低。体外子宫内膜上皮细胞（EECs）暴露GnRH-ant可降低CKB表达和ATP生成，并阻断肌动蛋白的聚合。此外，体外暴露于gnrh -ant的石川细胞表现出f -肌动蛋白解聚增强，而这些效应被CKB过表达所恢复。CKB敲除后观察到类似的效果，这些效果被CKB过表达所挽救。此外，与对照细胞相比，CKB敲除石川细胞的细胞迁移减少，这种影响也被CKB过表达所恢复。总之，这些发现表明GnRH-ant影响了ecs中CKB的表达，导致细胞骨架损伤和迁移失败。这些结果为GnRH-ant在子宫内膜治疗中的作用和分子机制提供了见解。
Some studies have demonstrated that the implantation rate of fresh transfer cycles is lower in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol than in the GnRH agonist (GnRH-a) protocol during in vitro fertilization (IVF). This effect may be related to endometrial receptivity. However, the mechanisms are unclear. Here, endometrial tissues obtained from the mid-secretory phase of patients treated with GnRH-a or GnRH-ant protocols and from patients on their natural cycle were assessed. Endometrial expression of B-type creatine kinase (CKB), which plays important roles in the implantation phase, was significantly reduced in the GnRH-ant group. At the same time, expression of the endometrial receptivity marker HOXA10 was considerably reduced in the GnRH-ant group. GnRH-ant exposure in endometrial epithelial cells (EECs) in vitro decreased CKB expression and ATP generation and blocked polymerization of actin. Furthermore, in vitro GnRH-ant-exposed Ishikawa cells showed enhanced F-actin depolymerization, and these effects were rescued by CKB overexpression. Similar effects were observed after CKB knockdown, and these effects were rescued by CKB overexpression. Moreover, cell migration was decreased in CKB-knockdown Ishikawa cells compared with that in control cells, and this effect was also rescued by CKB overexpression. Overall, these findings showed that GnRH-ant affected CKB expression in EECs, resulting in cytoskeletal damage and migration failure. These results provide insight into the roles and molecular mechanisms of GnRH-ant treatment in the endometrium.