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

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 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 eukḍaryotic 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. K E Y W O R D S dexamethasone, ERK1/2, implantation, mTOR, PP242, uterine receptivity How to cite this article: Shariati MBH, Niknafs B, Seghinsara AM, Shokrzadeh N, Alivand MR. 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.

Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity

“…miR-223-3p also suppresses the expression of leukemia inhibitory factor (LIF) during the implantation window in mouse uterus [46], a target that is essential for embryo implantation in both humans and mice [47,48]. A previous study confirms the upregulation of miR-223-3p in human endometrium with a compromised receptivity phenotype and its interaction with LIF [49]. In support, in our recent study we reveal that miR-223-3p is detected at low levels in the primary fertile human endometrial epithelial cells [50].…”

Noncanonical functions of glucocorticoids: A novel role for glucocorticoids in performing multiple beneficial functions in endometrial stem cells

“…However, glucocorticoids have recently been investigated as independent direct regulators of various uterine functions. For instance, Shariati et al found significantly decreased endometrial cell proliferation and a subsequent reduction in uterine receptivity during implantation in animals exposed to glucocorticoids by altering the expression of Muc1, SGK1, ENaC, miRNA 200a, and miRNA 223-3p via the ERK1/2-mTOR signaling pathway [ 50 ]. Similarly, Cooper et al observed a significant increase in the concentration of endometrial uterine NK cells in patients who had received synthetic glucocorticoid prednisolone [ 51 ].…”

BCL2L15 Depletion Inhibits Endometrial Receptivity via the STAT1 Signaling Pathway

“…Endometrial receptivity is a prerequisite to render the uterus suitable for embryo adhesion and to establish pregnancy in ruminants [18,19]. Although the molecular mechanism of regulating endometrial receptivity remains unclear, it is well-documented that altered gene expression in EECs during early pregnancy guarantees the success of embryo implantation [32]. Previous studies reported that exosomal proteins derived from day 17 pregnant ewes up-regulated BCL2L15 protein expression [10].…”