TGF-β1 and estradiol modulate prostaglandin concentrations and related gene expression in equine endometrium during the follicular phase.
Authors: Amaral Ana, Cerveira-Pinto Marta, Santos Carina, Kordowitzki Pawel, Skarzynski Dariusz, Ferreira-Dias Graça, Szóstek-Mioduchowska Anna
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary During the follicular phase of the oestrous cycle, transforming growth factor-beta 1 (TGF-β1) and 17β-oestradiol (E2) work synergistically to alter the endometrial balance between anti-fibrotic and pro-fibrotic prostaglandins, potentially explaining how chronic inflammatory conditions like endometrosis develop. Using explant tissue from equine endometrium, researchers measured mRNA expression and prostaglandin concentrations across 24 and 48-hour treatment periods, finding that combined TGF-β1 and E2 exposure significantly reduced PGE₂ (the anti-fibrotic mediator) whilst increasing PGF₂α (pro-fibrotic) at 48 hours—an unfavourable shift in the prostaglandin milieu. The combination treatment also upregulated receptors for PGE₂ (EP2 and EP4) whilst downregulating the PGF₂α receptor, suggesting a complex compensatory mechanism that ultimately favours fibrotic remodelling despite increased receptor expression for the protective prostaglandin. For equine practitioners, these findings suggest that endometrial fibrosis in mares may involve both hormonal and inflammatory pathways converging on prostaglandin metabolism, potentially opening avenues for targeted anti-inflammatory or prostaglandin-modulating therapies in mares with recurrent endometrosis or subfertility linked to endometrial degradation.
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Practical Takeaways
- •TGF-β1 and estradiol interact to suppress anti-fibrotic prostaglandin E2 pathways during the follicular phase, potentially explaining endometrial fibrosis progression in endometrosis cases
- •The shift toward pro-fibrotic PGF2α and away from anti-fibrotic PGE2 during the estrous cycle may represent a therapeutic window where targeted anti-fibrotic interventions could be beneficial
- •Understanding these hormonal and cytokine interactions may inform future treatment strategies for equine endometrosis, such as selective prostaglandin modulation during specific cycle phases
Key Findings
- •TGF-β1 and E2 combination treatment reduced PGE2 concentration at 48h compared to controls and TGF-β1 alone
- •PGF2α concentration increased with E2 at 24h and with TGF-β1/TGF-β1+E2 at 48h, shifting balance toward pro-fibrotic mediators
- •PTGS-2 mRNA was reduced by TGF-β1 and combination treatments at 24h, while PGFS mRNA reduced with TGF-β1 at 24h and E2 at 48h
- •EP2 and EP4 mRNA upregulated with combination treatment while FP receptor mRNA decreased in all treated groups