MiR-184 Combined with STC2 Promotes Endometrial Epithelial Cell Apoptosis in Dairy Goats via RAS/RAF/MEK/ERK Pathway.

Jiuzeng Cui,Sicheng Che,Xiaopeng An,Hongran Guo,Binyun Cao,Xiaorui Liu,Lichun Yang,Jincheng Han,Lei Zhang,Yuxuan Song,Zhongshi Zhu

doi:10.3390/genes11091052

Abstract

The endometrium undergoes a series of complex changes to form a receptive endometrium (RE) that allows the embryo to be implanted. The inability to establish endometrial receptivity of livestock causes embryo implantation failure and considerable losses to animal husbandry. MicroRNAs (miRNAs) are a class of noncoding RNAs. Studies have found that miRNAs can regulate many critical physiological processes, including the establishment of RE during embryo implantation. miR-184 is highly expressed in the endometrial receptive period of dairy goats. This study aimed to explore the effect of miR-184 on endometrial epithelial cell (EEC) apoptosis and RE establishment. Stanniocalcin2 (STC2) is a direct target of miR-184, and miR-184 decreases the expression of STC2 in dairy goat EECs. miR-184 can activate EECs apoptosis through the RAS/RAF/MEK/ERK pathway. Additionally, miR-184 increases the expression levels of RE marker genes, such as forkhead box M1 (FOXM1) and vascular endothelial growth factor (VEGF). These findings indicate that miR-184 promotes the apoptosis of endometrial epithelial cells in dairy goats by downregulating STC2 via the RAS/RAF/MEK/ERK pathway, and that it may also regulate the establishment of RE in dairy goats.

Highlights

Embryo implantation is a key step in mammalian reproduction [1]
The results showed that the expression of miR-184 in receptive endometrium (RE) increased by
Studies have shown that miR-184 promotes the apoptosis of trophoblast cells and inhibits their proliferation, which plays an important role in maintaining pregnancy [28]

Summary

Introduction

Embryo implantation is a key step in mammalian reproduction [1]. A series of complex dynamic changes in the endometrium eventually form a receptive endometrium (RE), and apoptosis of endometrial epithelial cells (EECs) is an essential step in this process [4,5]. In order to better understand embryo implantation in dairy goats, it is necessary to study the apoptosis of EECs. miRNAs are a class of endogenous noncoding RNAs which are generally involved in the regulation of posttranscriptional gene expression by indirect or direct inhibition of the translation of mRNA-bound. MiRNAs are involved in most biological processes in mammals, e.g., cell differentiation, proliferation and apoptosis [7]. Our previous studies showed that some miRNA regulates EEC apoptosis and proliferation, and participates in endometrial

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