Regulatory Effect of circRNA3890 on the Establishment of Receptive Endometrium in Dairy Goats

TL;DR

This study shows how circRNA3890 helps create a receptive environment in dairy goat endometrium for embryo implantation by regulating cell growth and signaling pathways.

Contribution

The study identifies a novel regulatory mechanism involving circRNA3890, miR-26b-3p, and MDM4 in endometrial receptivity in dairy goats.

Findings

circRNA3890 promotes endometrial epithelial cell proliferation by inhibiting miR-26b-3p.

MDM4 expression is upregulated through miR-26b-3p inhibition, enhancing endometrial receptivity.

miR-26b-3p regulates VEGFA and LIF, which are important for embryo implantation.

Abstract

Mammalian embryo implantation requires the endometrium to be in a receptive state. Many non-coding RNAs, such as circRNA3890, show differential expression between the receptive endometrium and pre-receptive endometrium of dairy goats, according to our earlier research. This work experimentally showed that circRNA3890 contributes to the establishment of receptive endometrium in dairy goats by controlling the proliferation and apoptosis of dairy goat endometrial epithelial cells (gEECs) by targeting miR-26b-3p/MDM4. These findings will contribute to understanding circRNA and miRNA function in embryo implantation and provide a theoretical basis for further improving the embryo attachment rate.

Receptive endometrium (RE) is essential for mammalian embryo implantation. The establishment of RE is a complex and precise dynamic process regulated by various cytokines, including non-coding RNAs (miRNAs, lncRNAs, and circRNAs). We identified candidate miR-26b-3p and circRNA3890 from our previous endometrial non-coding RNA sequencing data. CircRNA3890 adsorbs miR-26b-3p and inhibits its activity. Mouse double minute 4 (MDM4) is a target gene of miR-26b-3p, and circRNA3890 up-regulates the expression level of MDM4 by inhibiting the activity of miR-26b-3p in dairy goat endometrial epithelial cells (gEECs) in vitro. circRNA3890/miR-26b-3p/MDM4 could promote the proliferation of gEECs through the p53 signaling pathway. MiR-26b-3p could regulate the expression levels of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF) through MDM4 in gEECs, which contributes to the development of endometrial receptivity. Furthermore, the results showed that miR-26b-3p significantly promoted the development of RE and embryo implantation. These findings demonstrate that circRNA3890 targets and adsorbs miR-26b-3p to relieve MDM4 inhibition and promotes EEC proliferation through the p53 signaling pathway. They reveal the regulatory effect of miR-26b-3p on receptive endometrial development and embryo implantation in vitro and in vivo.

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