GnRH 拮抗剂通过减少 c-kit 的表达来抑制子宫内膜基质细胞的运动,从而影响胚胎植入过程。

IF 2 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Gynecological Endocrinology Pub Date : 2024-12-01 Epub Date: 2024-11-01 DOI:10.1080/09513590.2024.2421487
Jun Tan, Lu Fan, Xin Li, Lei-Zhen Xia, Ding-Fei Xu, Zhi-Qin Zhang, Chang-Hua Wang, Qiong-Fang Wu, Yan Zhao, Zeng-Ming Li
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引用次数: 0

摘要

背景:在体外受精-新鲜胚胎移植(IVF-ET)周期中,促性腺激素释放激素拮抗剂(GnRH-ant)方案与促性腺激素释放激素激动剂(GnRH-a)方案相比对临床结果有不利影响,这一点已得到公认。然而,相关机制尚不清楚:方法:对2014年1月至2021年9月期间在江西省妇幼保健院辅助生殖中心接受新鲜IVF-ET周期的18561例患者进行回顾性分析。采用倾向得分匹配(PSM)技术控制GnRH-ant组和GnRH-a组之间的混杂因素。收集人类子宫内膜基质细胞(hESCs)进行原代培养,并用相关受体拮抗剂和激活剂进行处理。采用 RT-PCR、Western Blot、免疫荧光染色、细胞迁移和粘附试验以及动物实验等方法阐明 GnRH 拮抗剂影响 hESCs 迁移和粘附能力的分子机制:结果:通过倾向评分匹配基础状态后,两组的基线特征无统计学差异。结果显示,子宫内膜厚度(10.4±2.35 mm vs. 11.03±2.61 mm,P vs. 50.36%,P vs. 72.7%,P vs. 65.24%,P vs. 56.1%,P vs. 9.04%,P 结论:GnRH-拮抗剂可降低 hESCs 的迁移和粘附能力:GnRH-ant可通过抑制C-kit受体的表达和活化来降低hESCs的运动能力,从而影响胚胎植入过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GnRH antagonist impairs the process of embryo implantation by inhibiting motility of endometrial stromal cells through reducing c-kit expression.

Background: It has been recognized that the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol has a detrimental effect on clinical outcomes compared to the GnRH agonist (GnRH-a) protocol during in vitro fertilization-fresh embryo transfer (IVF-ET) cycles. However, the related mechanisms were unclear.

Methods: A total of 18,561 patients, who underwent fresh IVF-ET cycles in the Center for Assisted Reproduction of Jiangxi Maternal and Child Health Hospital from January 2014 to September 2021, were retrospectively analyzed. The propensity score matching (PSM) technique was used to control for confounding factors between the GnRH-ant and GnRH-a groups. Human endometrial stromal cells (hESCs) were collected for primary culture and treated with relevant receptor antagonists and activators. RT-PCR, Western Blot, immunofluorescence staining, cell migration and adhesion assays, and animal experiments were employed to elucidate the molecular mechanism by which GnRH antagonist affects the migration and adhesion ability of hESCs.

Results: There was no statistical difference between the two groups in terms of baseline characteristics after matching basal status by propensity score matching. The result showed that the endometrial thickness (10.4 ± 2.35 vs. 11.03 ± 2.61 mm, p < .001) on trigger day was significantly lower in the GnRH-ant group. Compared with the GnRH-a protocol, the implantation rate (39.71% vs. 50.36%, p < .001), biochemical pregnancy rate (64.26% vs. 72.7%, p < .001), clinical pregnancy rate (56.39% vs. 65.24%, p < .001), live birth rate (45.25% vs. 56.1%, p < .001) in the GnRH-ant group were significantly decreased. Contrarily, the rate of early miscarriage in the GnRH-ant group (13.95% vs. 9.04%, p < .001) was higher than in the GnRH-a group. Furthermore, after treating with GnRH-ant, hESCs showed a reduced expression of HOXA10 and MMP-9 proteins, and a weakened migration ability. Subsequently, by establishing the co-culture system of hESCs and JAR trophoblast spheroids, we found that GnRH-ant inhibited the adhesion and invasion ability of trophoblast cells. Moreover, we also found a decreased expression and phosphorylation of c-kit receptor in decidualized hESCs after treating with GnRH-ant. Similar results as observed above were also confirmed when inhibiting the activation of c-kit receptor by imatinib.

Conclusions: GnRH-ant could reduce the motility of hESCs by inhibiting the expression and activation of the C-kit receptor, which impaired the process of embryo implantation.

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来源期刊
Gynecological Endocrinology
Gynecological Endocrinology 医学-妇产科学
CiteScore
4.40
自引率
5.00%
发文量
137
审稿时长
3-6 weeks
期刊介绍: Gynecological Endocrinology , the official journal of the International Society of Gynecological Endocrinology, covers all the experimental, clinical and therapeutic aspects of this ever more important discipline. It includes, amongst others, papers relating to the control and function of the different endocrine glands in females, the effects of reproductive events on the endocrine system, and the consequences of endocrine disorders on reproduction
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