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

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.

LncRNAs 60248.51 and 9826.1 are identified as potential regulators of endometrial receptivity in Tibetan Northwest Cashmere goats

“…A couple of epigenetic and transcriptomic analyses had revealed that kinase pathways may have important functions in regulating endometrial receptivity in the goat embryo (Liu et al, 2021;Song et al, 2019). Several in vitro studies indicated that MAPK and PI3K/AKT pathways play important roles in apoptosis and proliferation in goat stromal cells and endometrial epithelium cells, suggesting their involvement in goat endometrial receptivity (Cui et al, 2020;Liu et al, 2020;Zhang et al, 2018). Moreover, human clinical studies demonstrated that traditional Chinese medicines for assisted pregnancy, such as Xiaoyao powder and Bu Shen Zhu Yun Decoction, could improve human endometrial receptivity via growth cytokine-mediated activation of MAPK and PI3K/AKT pathways (He et al, 2022;Li et al, 2019).…”

miRNA profiling in intrauterine exosomes of pregnant cattle on day 7

“…MiR-184 has been reported to play roles in embryo implantation. In dairy goats, high throughput sequencing results of miRNA in the endometrial receptivity (RE) receptivity (PE) of dairy goats showed that the enrichment of miR-184 and RE was 31 times higher than that of PE ( P < 0.01) ( 39 ), and miR-184 promotes the apoptosis of endometrial epithelial cells by downregulating STC2 via the RAS/RAF/MEK/ERK pathway and is involved in the establishment of receptive endometrium ( 40 ).…”

RNA sequencing reveals dynamic expression of lncRNAs and mRNAs in caprine endometrial epithelial cells induced by Neospora caninum infection

“…These pathways have been reported to be involved in the regulation of important biological processes, such as cell proliferation, apoptosis, autophagy, inflammatory and immune response [75][76][77][78][79][80]. For example, upregulated expressions of lncRNA XR_001296952.2 and lncRNA XR_001919803.1 were found to cis-regulate the expression of stanniocalcin-2 (STC2), which could promote proliferation and inhibit apoptosis in caprine EECs through the RAS/RAF/MEK/ERK signaling pathways [81], and could also enhance autophagy through the PI3K/AKT/AMPK signaling pathways [82]. Previous studies have reported that activation of autophagy facilitated the proliferation of N. caninum both in vitro [35] and in vivo [83].…”