Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Science, Tabriz, Iran.
J Cell Physiol. 2019 Nov;234(11):19629-19639. doi: 10.1002/jcp.28562. Epub 2019 Apr 16.
Successful implantation of embryos requires endometrial receptivity. Glucocorticoids are one of the factors influencing the implantation window. In this study, 40 female BALB/c mice were used to study the impacts of dexamethasone administration on endometrial receptivity markers during implantation window. The mice mated and were randomly divided into four groups: control (vehicle), dexamethasone (100 μg/kg, IP), PP242 (30 mg/kg, IP), and dexamethasone + PP242 (Dex + PP242). On the Day 4th and 5th of gestation, mice received their respective treatments and were killed on the 5th day. To assess the expression of Muc1, leukemia inflammatory inhibitor (LIF), serum/glucocorticoid-inducible kinase 1 (SGK1), epithelial Na+ channel (ENaC), miRNA 200a, and miRNA 223-3p in the endometrium real-time polymerase chain reaction was performed. Furthermore, using Western blot analysis protein expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), mammalian target of rapamycin (mTOR), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) were evaluated. Periodic Acid-Schiff staining was used to examine the histomorphological changes of the uterus. According to the results dexamethasone declined the expression of LIF, whereas upregulated expression of Muc1, SGK1, ENaC mRNA, miRNA 200a, and miRNA 223-3p in the endometrium. In addition, PP242, an mTOR inhibitor, induced mRNA expression of Muc1, miRNA200a, and miRNa223-3p whereas it declined the expression of LIF. Moreover, activity of the ERK1/2-mTOR pathway in the endometrial cells was deterred by dexamethasone and PP242. Nonstop epithelium proliferation and elevated surface glycoproteins layer on epithelium of dexamethasone and/or PP242-received groups were divulged through histochemical analysis. According to the above mentioned results, uterine receptivity during implantation period was declined by dexamethasone, at least in part, through modulation of involved genes in endometrial receptivity and inhibition of the ERK1/2-mTOR pathway.
胚胎的成功着床需要子宫内膜的容受性。糖皮质激素是影响着床窗口的因素之一。在这项研究中，使用 40 只雌性 BALB/c 小鼠研究了在着床窗口期间给予地塞米松对子宫内膜容受性标志物的影响。这些小鼠交配后随机分为四组：对照组（载体）、地塞米松（100μg/kg，IP）、PP242（30mg/kg，IP）和地塞米松+PP242（Dex+PP242）。在妊娠第 4 天和第 5 天，各组小鼠接受相应的处理，并在第 5 天处死。为了评估子宫内膜中 Muc1、白血病炎症抑制剂（LIF）、血清/糖皮质激素诱导的激酶 1（SGK1）、上皮钠离子通道（ENaC）、miRNA200a 和 miRNA223-3p 的表达，采用实时聚合酶链反应进行检测。此外，通过 Western blot 分析评估细胞外信号调节激酶 1/2（ERK1/2）、哺乳动物雷帕霉素靶蛋白（mTOR）和真核翻译起始因子 4E 结合蛋白 1（4E-BP1）的蛋白表达。过碘酸希夫染色用于检查子宫的组织形态学变化。结果表明，地塞米松降低了 LIF 的表达，而子宫内膜中 Muc1、SGK1、ENaC mRNA、miRNA200a 和 miRNA223-3p 的表达上调。此外，mTOR 抑制剂 PP242 诱导 Muc1、miRNA200a 和 miRNa223-3p 的 mRNA 表达，而降低了 LIF 的表达。此外，地塞米松和 PP242 抑制了 ERK1/2-mTOR 通路在子宫内膜细胞中的活性。通过组织化学分析揭示了地塞米松和/或 PP242 处理组的上皮细胞持续增殖和上皮表面糖蛋白层升高。根据上述结果，地塞米松至少部分通过调节子宫内膜容受性相关基因和抑制 ERK1/2-mTOR 通路来降低着床期子宫的容受性。
