Regulation mechanism of miR-494-3p on endometrial receptivity in mice via PI3K/AKT/mTOR pathway

Abstract

Successful implantation requires endometrial receptivity. To investigate the mechanisms of miR-494-3p on endometrial receptivity, GnRHa's superovulation scheme was designed to reduce endometrial receptivity, and the pregnant mice were injected with miR-494-3p antagomir. The regulatory role of miR-494-3p was identified by RT-qPCR, uterine blastocyst count, scanning electron microscopy, hematoxylin-eosin (HE) staining, and Western blot. Results indicated that miR-494-3p antagomir increased uterine blastocysts numbers, promoted the pinocytosis expressions, and increased endometrial thickness. Besides, miR-494-3p antagomir significantly increased leukemia inhibitory factor (LIF), Ang-2 and VEGF protein expressions, and up-regulated p-AKT/AKT and p-mTOR/mTOR protein ratios in endometrium. Luciferase assay confirmed that LIF was a potential target of miR-494-3p. Subsequently, human endometrial epithelial cells (hEECs) were transfected with miR-494-3p inhibitor and PI3K inhibitor (LY294002). The role of miR-494-3p was identified by RT-qPCR, CCK-8 assay, transwell assay and flow cytometry. Results indicated that miR-494-3p inhibitor significantly increased proliferation and invasion, and significantly inhibited apoptosis in hEECs, while LY294002 reversed its biological function. Overall, these results suggested that miR-494-3p is the key regulator of endometrial receptivity in mice, regulating this complex process through the PI3K/AKT/mTOR pathway. Understanding the role of miR-494-3p in endometrial receptivity is of great significance for exploring new targets for the diagnosis and treatment of early pregnancy failure, and improving the success rates of artificial reproduction.

TJZYF Improves Endometrial Receptivity through Regulating VEGF and PI3K/AKT Signaling Pathway

“…Zhao et al found that positive correlation of VEGF and the endometrial receptivity in PCOS rats and that VEGF could be a therapeutic target for PCOS [ 41 ]. Furthermore, the recent study has demonstrated that miR-494-3p is of great importance in endometrial receptivity through PI3K/Akt/mTOR pathway [ 42 ]. However, whether TJZYF is efficient and play a role through VEGF, PI3K/Akt pathway in improving endometrial receptivity is not reported before.…”

Screening of Differentially Expressed Genes and miRNAs in Hypothalamus and Pituitary Gland of Sheep under Different Photoperiods

“…Among them, miR-200a is a member of the miR-200 family, which is associated with ovarian development in goats [ 37 ]. One study showed that miR-494-3p significantly inhibited apoptosis of endometrial epithelial cells [ 38 ], and oar-miR-485-3p can regulate the developmental quality of oocytes [ 39 ]. From the above, we can speculate that DEMs target and regulate genes related to reproductive estrus, which may be responsible for the reproductive variation in sheep due to different photoperiodic changes.…”

Effects of N Acetylcysteine on the Expression of Genes Associated with Reproductive Performance in the Goat Uterus during Early Gestation

“…NM23 can affect metaphase by regulating mouse and human endometrial stromal cells via the PI3K-Akt-mTOR signalling pathway [ 52 ]. miR-494-3p regulates endometrial receptivity in mice via the PI3K/AKT/mTOR pathway [ 53 ]. Our preliminary data suggest that the PI3K/Akt signalling pathway is enriched in the most DEGs compared with other signalling pathways.…”