Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
J Cell Physiol. 2019 Nov;234(11):20098-20110. doi: 10.1002/jcp.28609. Epub 2019 Apr 9.
Implantation of embryos needs endometrial receptivity. Mineralocorticoids is one of the causes influencing the implantation window. This study targeted to evaluation fludrocortisone different properties on endometrial receptivity. The objective of this study was to assess whether treatment with fludrocortisone could impact the expression of diverse genes and proteins that are involved in uterine receptivity in mice. In this study, 40 female adult BALB/c mice were used. The samples were allocated to four groups of ten. Control group (C) received: vehicle; fludrocortisone group (FCA): received 1.5 mg/kg fludrocortisone; PP242 group (PP242): received 30 mg/kg PP242; fludrocortisone+PP242 group (FCA+PP242): received fludrocortisone and PP242. Mice were killed on window implantation day after mating and confirmed pregnancy. The endometrial epithelium of mouse was collected to assess mRNA expression of leukemia inhibitory factor (LIF), mucin-1 (MUC1), heparin-binding epidermal growth factor (HB-EGF), (Msx.1), miRNA Let-7a, and miRNA 223-3p as well as protein expression 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) in the uterine using real-time PCR and western blot, respectively. In comparison with the control group, fludrocortisone administration upregulated the expression of LIF, HB-EGF, Msx.1, miRNA Let-7a, ERK1/2, and mTOR in the epithelial endometrium. The PP242-treated group demonstrated a significant rise in the expression of MUC1, miRNA 223-3p and a remarkable decline in ERK1/2 and p-4E-BP1 levels in comparison with the control group. Combination therapy of (FCA+PP242) resulted in a remarkable rise in LIF, Msx-1, HB-EGF, ERK1/2, and mTOR levels, in comparison with the PP242 group. Furthermore, combination therapy of (FCA+PP242) downregulated the expression of MUC1 in comparison with the PP242-treated group. According to the results, fludrocortisone affected uterine receptivity possibly by means of modulating the expression of genes involved in the uterine receptivity and activation of the ERK1/2-mTOR pathway.
胚胎着床需要子宫内膜容受性。盐皮质激素是影响着床窗口的原因之一。本研究旨在评估氟氢可的松对子宫内膜容受性的不同特性。本研究的目的是评估氟氢可的松治疗是否会影响参与小鼠子宫容受性的不同基因和蛋白质的表达。在这项研究中，使用了 40 只成年雌性 BALB/c 小鼠。将样本分为四组，每组 10 只。对照组（C）接受：载体；氟氢可的松组（FCA）：接受 1.5mg/kg 氟氢可的松；PP242 组（PP242）：接受 30mg/kg PP242；氟氢可的松+PP242 组（FCA+PP242）：接受氟氢可的松和 PP242。交配后，在着床窗口当天杀死小鼠并确认怀孕。收集小鼠子宫内膜上皮以评估白血病抑制因子（LIF）、粘蛋白-1（MUC1）、肝素结合表皮生长因子（HB-EGF）、（Msx.1）、miRNA Let-7a 和 miRNA 223-3p 的 mRNA 表达以及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，分别采用实时 PCR 和 Western blot。与对照组相比，氟氢可的松给药可上调上皮子宫内膜中 LIF、HB-EGF、Msx.1、miRNA Let-7a、ERK1/2 和 mTOR 的表达。与对照组相比，PP242 处理组 MUC1、miRNA 223-3p 的表达显著升高，ERK1/2 和 p-4E-BP1 水平显著降低。与 PP242 组相比，（FCA+PP242）联合治疗可显著升高 LIF、Msx-1、HB-EGF、ERK1/2 和 mTOR 水平。此外，与 PP242 治疗组相比，（FCA+PP242）联合治疗可下调 MUC1 的表达。根据结果，氟氢可的松可能通过调节参与子宫容受性的基因表达和激活 ERK1/2-mTOR 途径来影响子宫容受性。
