Abstract
BackgroundN-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.MethodsUterine 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.ResultsUterine 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.ConclusionsThese results suggest that NDRG2 might play an important role in the process of decidualization during early pregnancy.
Highlights
N-myc down-regulated gene 2 (NDRG2) is a tumor suppressor involved in cell proliferation and differentiation
Uterine NDRG2 expression during the estrous cycle and peri-implantation period The uterine expression patterns of NDRG2 mRNA and NDRG2 protein during the mouse estrous cycle were determined by real-time PCR and IHC, respectively
Prior to the initiation of implantation, uterine NDRG2 mRNA expression gradually increased from day 1 (D1) to day 4 (D4) of pregnancy
Summary
N-myc down-regulated gene 2 (NDRG2) is a tumor suppressor involved in cell proliferation and differentiation. During mouse fetal development, NDRG2 has been found to be strongly expressed in various tissues and organs [12], suggesting its potential role in embryonic development. This gene is phosphorylated by protein kinase B (PKB/Akt), PKC [13], and glucocorticoid-induced kinase 1 (SGK1) [14]. We hypothesized that NDRG2 might be involved in the process of embryo implantation, and the present study was undertaken to examine the uterine expression pattern of this gene during the estrous cycle and peri-implantation period in mice
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