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

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 that infection 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 that infection significantly promoted the secretion of PGD in BMDMs. In the early stage of infection, ELISA results showed that exogenous PGD significantly 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 PGD markedly 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 PGD enhanced the intracellular survival of in macrophages. H&E staining showed that PGD exacerbated pathological damage in bovine endometrial tissues. Contrastingly, at later stages, PGD suppresses the expression of inflammatory mediators, decreases survival, 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.