Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions.
Authors: Amaral Ana, Fernandes Carina, Rebordão Maria Rosa, Szóstek-Mioduchowska Anna, Lukasik Karolina, Pinto-Bravo Pedro, Telo da Gama Luís, Jan Skarzynski Dariusz, Ferreira-Dias Graça
Journal: Animals : an open access journal from MDPI
Summary
# Editorial Summary: Myeloperoxidase Inhibition and Endometrial Fibrosis in Mares Endometrosis—chronic fibrotic degeneration of the mare's endometrium—involves neutrophil-mediated inflammation, particularly through neutrophil extracellular traps (NETs) that release myeloperoxidase (MPO). This in vitro study investigated whether inhibiting MPO with 4-aminobenzoic acid hydrazide (ABAH) could reduce the pro-fibrotic cascade in endometrial tissue by suppressing collagen deposition and metallopeptidase activity. Endometrial explants from mares were treated with MPO, ABAH, or both for 24–48 hours across different reproductive phases, with gene expression (qPCR), protein abundance (Western blot), and enzyme activity (zymography) measured to assess collagen type I and matrix metallopeptidases (MMP-2/-9). MPO significantly elevated collagen I protein in follicular phase tissue; critically, ABAH successfully suppressed this collagen induction at 48 hours. MMP-2 activity spiked acutely in mid-luteal phase following MPO exposure but was reduced when ABAH was co-administered, whilst MMP-9 activation in response to prolonged MPO was inhibited by ABAH in follicular phase at 48 hours. These findings suggest that blocking MPO-driven inflammation could interrupt the fibrotic remodelling underlying endometrosis, with MMP-2 functioning as an acute-phase responder and MMP-9 responding to sustained neutrophil activity—implications that warrant investigation of MPO inhibition as a therapeutic strategy to preserve endometrial function and fertility in susceptible mares.
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Practical Takeaways
- •MPO inhibition via ABAH may represent a novel therapeutic strategy to reduce fibrosis development in endometrosis by suppressing collagen deposition and metallopeptidase activity
- •The response to MPO varies by estrous cycle phase, with follicular phase showing prolonged MMP-9 activation and mid-luteal phase showing acute MMP-2 activation, suggesting cycle-dependent treatment timing may be relevant
- •Further in vivo studies are needed to determine clinical applicability of MPO inhibition for managing endometrosis in breeding mares
Key Findings
- •Myeloperoxidase (MPO) elevated collagen type I protein abundance in follicular phase endometrial explants at both 24 and 48 hours
- •ABAH successfully inhibited MPO-induced collagen type I expression in follicular phase at 48 hours
- •MMP-2 gelatinolytic activity increased in mid-luteal phase at 24 hours after MPO treatment but was reduced with ABAH co-treatment
- •MMP-9 active form activity was elevated by MPO treatment and inhibited by ABAH in follicular phase at 48 hours