TGF-β1 and estradiol modulate prostaglandin concentrations and related gene expression in equine endometrium during the follicular phase.

Transforming growth factor (TGF)-β1 is a pro-fibrotic cytokine that affects extracellular matrix (ECM) deposition and fibroblast activity. 17β-Estradiol (E2), the dominant ovarian steroid during the follicular phase (FLP) of the estrous cycle, can also influence ECM remodeling and fibrosis, through prostaglandin (PG) synthesis. PGs have opposing roles in fibrosis, with PGE₂ showing anti-fibrotic effects and PGF₂α promoting fibrosis. Equine endometrosis, whose main pathological feature is fibrosis, is marked by chronic inflammation and ECM accumulation, and may involve mediators like TGF-β1, PGs, and E2. This study aimed to assess how TGF-β1, E2, and their combination affect PG synthase and receptors transcription (qPCR) and PG concentrations (ELISA) in equine endometrial explants during the FLP, after 24 and 48 h. Prostaglandin-endoperoxide synthase 2 (PTGS-2) mRNA was reduced with TGF-β1 and combination treatments at 24 h. Estradiol and combined treatments downregulated microsomal prostaglandin E synthase1 (PGES) mRNA at 24 h, while prostaglandin F synthase (PGFS) mRNA reduced with TGF-β1 at 24 h and with E2 at 48 h. The PGE₂ concentration was lower in TGF-β1 +E2 group than in controls and TGF-β1 alone at 48 h. In contrast, PGF₂α concentration increased with E2 at 24 h and TGF-β1 and TGF-β1 +E2 treatments at 48 h. Prostaglandin E receptor (EP)2 and 4 mRNA upregulated with the combination treatment, while prostaglandin F receptor (FP) mRNA decreased in all treated groups. These findings suggest that TGF-β1 and E2 interact to regulate PG pathways, with potential to drive fibrotic changes in the equine endometrium, by shifting the balance between anti- and pro-fibrotic mediators like PGE₂ and PGF₂α.