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J Cell Physiol


Title:"Administration of dexamethasone disrupts endometrial receptivity by alteration of expression of miRNA 223, 200a, LIF, Muc1, SGK1, and ENaC via the ERK1/2-mTOR pathway"
Author(s):Shariati MBH; Niknafs B; Seghinsara AM; Shokrzadeh N; Alivand MR;
Address:"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. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran. Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Department of Genetic, Facualty of Medcine, Tabriz University of Medical Sciences, Tabriz, Iran"
Journal Title:J Cell Physiol
Year:2019
Volume:20190416
Issue:11
Page Number:19629 - 19639
DOI: 10.1002/jcp.28562
ISSN/ISBN:1097-4652 (Electronic) 0021-9541 (Linking)
Abstract:"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 mug/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"
Keywords:"Animals Cell Proliferation/*drug effects Dexamethasone/*pharmacology Embryo Implantation/*drug effects/genetics Endometrium/*drug effects Epithelial Sodium Channels/genetics Female Gene Expression Regulation, Developmental/drug effects Humans Immediate-Ea;"
Notes:"MedlineShariati, Mohammad Bakhtiar Hesam Niknafs, Behrooz Seghinsara, Abbas Majdi Shokrzadeh, Naser Alivand, Mohammad Reza eng Research Support, Non-U.S. Gov't 2019/04/18 J Cell Physiol. 2019 Nov; 234(11):19629-19639. doi: 10.1002/jcp.28562. Epub 2019 Apr 16"

 
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