Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiaotong University, School of Medicine, Shanghai Key Laboratory of Reproductive Medicine, Huangpu, Shanghai, China.
Center of Reproductive Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Huangpu, Shanghai, China.
Reproduction. 2020 May;159(6):733-743. doi: 10.1530/REP-19-0578.
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.
一些研究表明，在体外受精（IVF）中，促性腺激素释放激素拮抗剂（GnRH-ant）方案的新鲜移植周期的着床率低于促性腺激素释放激素激动剂（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 方案治疗的患者以及自然周期患者的子宫内膜组织。在 GnRH-ant 组中，B 型肌酸激酶（CKB）的表达显著降低，CKB 在着床期发挥重要作用。同时，在 GnRH-ant 组中，子宫内膜容受性标志物 HOXA10 的表达也明显降低。体外 GnRH-ant 暴露于子宫内膜上皮细胞（EEC）中降低了 CKB 的表达和 ATP 的产生，并阻断了肌动蛋白的聚合。此外，体外 GnRH-ant 暴露的 Ishikawa 细胞显示 F-肌动蛋白解聚增强，而 CKB 过表达可挽救这些作用。CKB 敲低后也观察到类似的作用，而 CKB 过表达可挽救这些作用。此外，与对照细胞相比，CKB 敲低的 Ishikawa 细胞的细胞迁移减少，而 CKB 过表达可挽救这种作用。总之，这些发现表明 GnRH-ant 影响 EECs 中的 CKB 表达，导致细胞骨架损伤和迁移失败。这些结果为 GnRH-ant 治疗在子宫内膜中的作用和分子机制提供了新的认识。
