Lipopolysaccharide stimulates bovine endometrium explants through toll‑like receptor 4 signaling and PGE₂ synthesis

Bovine endometrium infection with gram-negative bacteria commonly causes uterine diseases. Previous studies indicate that prostaglandin E₂ (PGE₂) is an inflammatory mediator in bacterial endometritis. However, the mechanism underlying lipopolysaccharide (LPS)-induced inflammatory response regulation in bovine endometrial explants remains elusive. In the present study, bovine explants were pre-treated with 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors before LPS stimulation. PGE₂ secretion, prostaglandin synthetase, pro-inflammatory factor, damage-associated molecular pattern (DAMP), and related signaling pathway factor levels were evaluated. Using 15-PGDH inhibitors pre-treatment, LPS-treated bovine endometrial explants exhibited augmentation of PGE₂ and DAMP expression, and upregulation of various signaling pathway factors. Protein kinase A (PKA), extracellular-signal-regulated kinase, and c-Jun N-terminal kinase phosphorylation and degradation of nuclear transcription factor-κB (NF-κB) inhibitors were induced in the pre-treated endometrial explants. The mechanism underlying LPS-induced PGE₂ accumulation acting as a pro-inflammatory mediator through toll-like receptor 4 signaling in bovine explants could involve the PKA, mitogen-activated protein kinase, and NF-κB pathways.