Gu Yan, Zhang Xuan, Yang Qian, Wang Jian-mei, He Ya-ping, Sun Zhao-gui, Zhang Hui-qin, Wang Jian
Shanghai Medical School, Fudan University, Shanghai, China.
NPFPC Key Laboratory of Contraceptive Drugs & Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, China.
Reprod Biol Endocrinol. 2015 May 27;13:49. doi: 10.1186/s12958-015-0047-7.
N-myc down-regulated gene 2 (NDRG2) is a tumor suppressor involved in cell proliferation and differentiation. The aim of this study was to determine the uterine expression pattern of this gene during early pregnancy in mice.
Uterine NDRG2 mRNA and protein expression levels were determined by RT-PCR and Western blot analyses, respectively, during the peri-implantation period in mice. Immunohistochemical (IHC) analysis was performed to examine the spatial localization of NDRG2 expression in mouse uterine tissues. The in vitro decidualization model of mouse endometrial stromal cells (ESCs) was used to evaluate decidualization of ESCs following NDRG2 knock down by small interfering RNA (siRNA). Statistical significance was analyzed by one-way ANOVA using SPSS 19.0 software.
Uterine NDRG2 gene expression was significantly up-regulated and was predominantly localized to the secondary decidual zone on days 5 and 8 of pregnancy in mice. Its increased expression was associated with artificial decidualization as well as the activation of delayed implantation. Furthermore, uterine NDRG2 expression was induced by estrogen and progesterone treatments. The in vitro decidualization of mouse ESCs was accompanied by up-regulation of NDRG2 expression, and knock down of its expression in these cells by siRNA inhibited the decidualization process.
These results suggest that NDRG2 might play an important role in the process of decidualization during early pregnancy.
N-myc下游调节基因2(NDRG2)是一种参与细胞增殖和分化的肿瘤抑制因子。本研究旨在确定该基因在小鼠早期妊娠期间子宫中的表达模式。
分别通过逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析,测定小鼠着床期子宫中NDRG2 mRNA和蛋白质的表达水平。采用免疫组织化学(IHC)分析检测NDRG2在小鼠子宫组织中的表达空间定位。利用小鼠子宫内膜基质细胞(ESC)的体外蜕膜化模型,评估小干扰RNA(siRNA)敲低NDRG2后ESC的蜕膜化情况。使用SPSS 19.0软件通过单因素方差分析进行统计学显著性分析。
小鼠妊娠第5天和第8天,子宫NDRG2基因表达显著上调,且主要定位于次级蜕膜区。其表达增加与人工蜕膜化以及延迟着床的激活有关。此外,雌激素和孕激素处理可诱导子宫NDRG2表达。小鼠ESC的体外蜕膜化伴随着NDRG2表达上调,siRNA敲低这些细胞中的NDRG2表达可抑制蜕膜化过程。
这些结果表明,NDRG2可能在早期妊娠蜕膜化过程中发挥重要作用。