HOXA10 regulates apoptosis and expression of receptivity-related genes in bovine endometrial epithelial cells

HOXA10 is a crucial marker gene for endometrial receptivity in mammals, with significantly increased expression in endometrial epithelial cells during the implantation window. However, the molecular mechanisms by which HOXA10 regulates bovine endometrial epithelial cells remain unclear. In this study, we constructed RNA interference fragments targeting the bovine HOXA10 gene, transfected them into bovine endometrial epithelial cells, and performed RNA-seq analysis. We conducted EdU staining, flow cytometry, RT-qPCR, and Western blot to assess apoptosis and the FOXO1 signaling pathway. Additionally, RT-qPCR, Western blot, and immunofluorescence staining were used to analyze the expression of genes associated with receptivity (ITGB3, ITGB6, ITGAV, and MUC1). The results showed that HOXA10 interference induced apoptotic changes in bovine endometrial epithelial cells. Metabolic pathways differentially affected included the cell cycle, cellular senescence, the FOX signaling pathway, and DNA replication. The expression levels of FOXO1, CDKN1A, CCND1, CDK4, and BAX were significantly upregulated, while CCNE1, CCNB1, CDK2, and BCL-2 were significantly downregulated. Furthermore, the mRNA expression of ITGB3, ITGB6, and ITGAV was significantly reduced, while MUC1 mRNA expression was significantly increased. Therefore, these findings indicate that the HOXA10 interference activates the FOXO1 pathway, leading to apoptosis in bovine endometrial epithelial cells.