Exogenous prostaglandin Das a modulator in bovine endometritis: implications for reducing antibiotic use in dairy cattle.

Abstract

INTRODUCTION: Bovine endometritis is a common postpartum uterine infection that significantly impacts the health and production performance of dairy cows, leading to economic losses for farms. Bovine endometritis is closely associated with pathogenic microorganisms, disturbances in uterine microecology, and localized inflammatory damage.() is the primary pathogenic bacterium responsible for bovine endometritis. Prostaglandin D(PGD) is abundant in the uterine environment. However, its role in-induced endometritis remains largely unknown. We used bovine bone marrow-derived macrophages (BMDMs) and bovine endometrial tissue to investigate the specific genes and molecular mechanisms involved in-induced bovine endometritis. METHODS AND RESULTS: Transcriptomic data show thatinfection significantly upregulated 2,141 genes and downregulated 2,381 genes in bovine BMDMs.activates various molecular functions in bovine BMDMs, with the most closely related being the inflammatory response, in which Prostaglandin-Endoperoxide Synthase 2 (PTGS2) plays a crucial role. Additionally, ELISA analysis revealed thatinfection significantly promoted the secretion of PGDin BMDMs. In the early stage of infection, ELISA results showed that exogenous PGDsignificantly promoted the secretion of TNF-α, IL-1β, and IL-6 in BMDMs and endometrial tissues, suggesting its role in enhancing the inflammatory response during early infection. Further q-PCR and immunofluorescence analyses demonstrated that PGDmarkedly upregulated the expression of damage-associated molecules, including high mobility group box 1 (HMGB-1) and hyaluronic acid-binding protein 2 (HABP-2). In addition, immunofluorescence and MTT assay results indicated that PGDenhanced the intracellular survival ofin macrophages. H&E staining showed that PGDexacerbated pathological damage in bovine endometrial tissues. Contrastingly, at later stages, PGDsuppresses the expression of inflammatory mediators, decreasessurvival, and alleviates tissue damage. DISCUSSION: These results not only deepen our understanding of the multifaceted role of exogenous PGD2 in uterine pathophysiology but also provide potential therapeutic implications for the treatment of bovine endometritis.