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Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression.
Systems Biology in Reproductive Medicine ( IF 2.4 ) Pub Date : 2019-10-02 , DOI: 10.1080/19396368.2019.1671536
Jingtao Shen 1, 2 , Xudong Zhu 3 , Mei Zhang 1, 2 , Yue Jiang 1 , Guijun Yan 1 , Zhilong Wang 1 , Lihua Sun 4 , Qun Zhang 1
Affiliation  

HOXA10 is an important regulator of embryo adhesion. Reduced expression may contribute to embryo implantation failure. The expression of Nur77 and HOXA10 has been shown to be reduced in the endometrium of patients with recurrent implantation failure. In this study, we found that Nur77 was directly bound to the HOXA10 promoter and promoted HOXA10 protein expression in a dose-dependent manner in Ishikawa cells. Furthermore, the promoting effect of Nur77 on embryo adhesion was significantly blocked when endogenous HOXA10 expression was knocked down in Ishikawa cells. Moreover, the Nur77 agonist 6-MP was also confirmed to promote embryo adhesion. This study is the first to show that Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression. Nur77 and 6-MP may provide a basis to develop a new treatment for patients who suffer from embryo adhesion dysfunction. Abbreviations: HB-EGF: heparin-binding epidermal growth factor-like growth factor; HOXA10: homeobox A10; NGFI-B: nerve growth factor-induced gene B; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; 6-MP: 6-mercaptopurine; IGFBP-1: insulin-like growth factor binding protein-1; LIF: leukemia inhibitory factor; IL-1β: Interleukin - 1β; CRISPR/Cas9: Clustered Regularly Interspaced Short Palindromic Repeats; AF-1: activation function-1 domain; HIF-1α: hypoxia-inducible factor 1α; CREB: cAMP response element binding.

中文翻译:

Nur77通过转录调节HOXA10表达来促进胚胎粘附。

HOXA10是胚胎粘附的重要调节剂。表达降低可能导致胚胎植入失败。Nur77和HOXA10的表达在反复植入失败的患者子宫内膜中被证明降低。在这项研究中,我们发现Nur77直接与HOXA10启动子结合并以剂量依赖的方式促进了石川细胞中HOXA10蛋白的表达。此外,当在石川细胞中敲低内源性HOXA10表达时,Nur77对胚胎粘附的促进作用被显着阻断。此外,还证实了Nur77激动剂6-MP促进胚胎粘附。这项研究首次表明Nur77通过转录调节HOXA10表达来促进胚胎粘附。Nur77和6-MP可能为开发新的治疗患有胚胎黏附功能障碍的患者的基础。缩写:HB-EGF:肝素结合表皮生长因子样生长因子;HOXA10:homeobox A10;NGFI-B:神经生长因子诱导基因B;RIF:反复植入失败;RPL:反复流产;6-MP:6-巯基嘌呤; IGFBP-1:胰岛素样生长因子结合蛋白-1;LIF:白血病抑制因子;IL-1β:白介素-1β;CRISPR / Cas9:簇状规则间隔的短回文重复序列;AF-1:激活功能1域;HIF-1α:缺氧诱导因子1α;CREB:cAMP反应元件结合。反复植入失败;RPL:反复流产;6-MP:6-巯基嘌呤; IGFBP-1:胰岛素样生长因子结合蛋白-1;LIF:白血病抑制因子;IL-1β:白介素-1β;CRISPR / Cas9:簇状规则间隔的短回文重复序列;AF-1:激活功能1域;HIF-1α:缺氧诱导因子1α;CREB:cAMP反应元件结合。反复植入失败;RPL:反复流产;6-MP:6-巯基嘌呤; IGFBP-1:胰岛素样生长因子结合蛋白-1;LIF:白血病抑制因子;IL-1β:白介素-1β;CRISPR / Cas9:簇状规则间隔的短回文重复序列;AF-1:激活功能1域;HIF-1α:缺氧诱导因子1α;CREB:cAMP反应元件结合。
更新日期:2019-11-01
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