Aging-associated transcriptomic changes in the bovine endometrium

Proper endometrial function is essential for fertility, but aging impairs endometrial activity through mechanisms that remain unclear in cattle. This study aimed to identify age-related differentially expressed genes (DEGs) in the endometrium of approximately 121-month-old multiparous Japanese Black cows (N = 5) compared with approximately 24-month-old nulliparous heifers (N = 5), using RNA sequencing. A total of 20,285 and 26,241 annotated genes were expressed in the intercaruncular (ICAR) and caruncular (CAR) regions, respectively. In aged cows, 350 genes showed higher and 84 lower expression in the ICAR, while 280 were higher and 156 lower in the CAR (P < 0.01, fold change >20 %). In total, 434 and 436 genes were identified as DEGs in ICAR and CAR respectively, including growth factors, receptors, and orphan G-protein-coupled receptors. Metascape analysis of ICAR DEGs revealed enrichment in pathways related to cell growth, growth factor response, lipid biosynthetic, negative regulation of cell adhesion and differentiation, and embryonic morphogenesis. CAR DEGs were enriched in collagen-associated and epithelial differentiation pathways. Ingenuity Pathway Analysis (IPA) of ICAR DEGs highlighted networks involving oxidative stress-induced senescence, arachidonic acid metabolism, epithelial adherens junction signaling, and tight junction signaling, as well as canonical pathways of G-protein-coupled receptor signaling, and glycosaminoglycan metabolism (P < 0.01). IPA of CAR DEGs indicated enrichment in nonsense mediated decay, collagen chain trimerization, and wound healing signaling pathway. These findings identify DEGs and signaling pathways associated with aging in the bovine endometrium.