GnRH antagonist weakens endometrial stromal cells growth ability by decreasing c-kit receptor expression.
GnRH antagonist weakens endometrial stromal cells growth ability by decreasing c-kit receptor expression.
复制标题
DOI：
10.1186/s12958-021-00886-y
复制
发表时间：
2022-02-04
期刊：
影响因子：
--
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Xu DF;Liu PP;Fan L;Xie Q;Zhang ZQ;Wang LQ;Wu QF;Tan J
一些研究报道，在体外受精-新鲜胚胎移植过程中，使用促性腺激素释放激素拮抗剂(GnRH-ANT)方案的患者与使用GnRH激动剂(GnRH-a)方案的患者相比，植入率和临床妊娠率显著降低。随后的研究将这一不良结果归因于促性腺激素释放激素-ANT对子宫内膜容受性的负面影响。然而，这些机制还没有完全被理解。对我中心2815例新鲜胚胎移植患者的临床资料进行分析。用促性腺激素释放激素类似物或伊马替尼(c-Kit受体抑制剂)处理8-10 孕周正常妊娠终止妊娠的健康妇女子宫内膜间质细胞。用CCK8和流式细胞仪检测胚胎干细胞的生长能力。免疫荧光染色和免疫印迹法检测目的蛋白。临床资料显示，GnRH-ANT组HCG日子宫内膜厚度明显低于对照组。虽然两组胚胎质量无明显差异，但GnRH-ANT组的HCG阳性率、胚胎着床率和妊娠率均显著低于对照组。此外，GnRH-ANT还能显著抑制ESCs的增殖并诱导其凋亡。此外，GnRH-ANT还显著降低了在胚胎着床过程中起关键作用的c-kit受体的表达和激活。伊马替尼抑制c-kit的激活可显著抑制ESCs的增殖和促进其凋亡。此外，与细胞生长密切相关的AKT的磷酸化和Cyclin D1的表达在伊马替尼处理后明显减少。综上所述，我们的研究表明，GnRH-ANT通过减少c-kit受体的表达来减弱c-kit受体的激活，导致ESCs的生长能力受损。我们的发现为了解促性腺激素释放激素-ANT对子宫内膜的影响提供了新的视角。网上版载有补充材料，可在10.1186/s12958-021-00886-y查阅。
Several surveys have reported that patients treated with gonadotropin-releasing hormone antagonist (GnRH-ant) protocol showed a significantly lower rate of implantation and clinical pregnancy compared to GnRH agonist (GnRH-a) protocol during in vitro fertilization-fresh embryo transfer. Subsequent studies imputed this poor outcome to the negative effects of GnRH-ant on endometrial receptive. However, the mechanisms were not fully understood. The clinical data of 2815 patients undergoing fresh embryo transfer in our center were analyzed. Human endometrial stromal cells (ESCs) from healthy women undergoing elective pregnancy termination of a normal pregnancy at 8–10 weeks gestation were treated with GnRH-analogs or imatinib (c-kit receptor inhibitor). CCK8 and Flow cytometry were used to investigated the growth ability of ESCs. Immunofluorescence staining and western blot was used to detected the target proteins. The clinical data showed that the endometrial thickness on HCG Day were significantly lower in GnRH-ant group. Although no difference of embryo quality in these two groups, GnRH-ant group showed remarkably decreased rate of HCG positive, embryo implantation and pregnancy. Moreover, GnRH-ant significantly reduced the proliferation and induced the apoptosis of ESCs. Furthermore, the expression and activation of c-kit receptor, which played pivotal roles during embryo implantation, were observably decreased by GnRH-ant. Inhibiting the activation of c-kit by imatinib remarkably suppressed the proliferation and promoted the apoptosis of ESCs. Additionally, the phosphorylation of AKT and expression of Cyclin D1, which were closely related with cellular growth, were distinctly lessened after treating with imatinib. In summary, our study showed that GnRH-ant weakened the activization of c-kit receptor by decreasing its expression, causing the impaired growth ability of ESCs. Our findings provided a new insight into the effects of GnRH-ant on endometrium. The online version contains supplementary material available at 10.1186/s12958-021-00886-y.
登录
查看更多内容
DOI：
10.1093/humrep/dey281
发表时间：
2018-10-01
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Liu KE;Hartman M;Hartman A;Luo ZC;Mahutte N
通讯作者：
Mahutte N
影响因子：
9.2
作者：
Liang J;Wu YL;Chen BJ;Zhang W;Tanaka Y;Sugiyama H
通讯作者：
Sugiyama H
影响因子：
6.7
作者：
Amir, Wiser;Micha, Baum;Adrian, Shulman
通讯作者：
Adrian, Shulman
影响因子：
4
作者：
Gallos, Ioannis D.;Khairy, Mohammed;Coomarasamy, Arri
通讯作者：
Coomarasamy, Arri
影响因子：
6.1
作者：
Ortmann, O;Diedrich, K
通讯作者：
Diedrich, K