Lysophosphatidic acid as a regulator of endometrial connective tissue growth factor and prostaglandin secretion during estrous cycle and endometrosis in the mare.
Authors: Szóstek-Mioduchowska Anna, Leciejewska Natalia, Zelmańska Beata, Staszkiewicz-Chodor Joanna, Ferreira-Dias Graça, Skarzynski Dariusz
Journal: BMC veterinary research
Summary
# Editorial Summary Endometrosis—the progressive fibrotic degeneration of the mare's endometrium—significantly compromises fertility, yet the underlying cellular mechanisms remain incompletely understood. Sóstek-Mioduchowska and colleagues investigated whether lysophosphatidic acid (LPA), a lipid signalling molecule, drives fibrotic changes in endometrosis by examining endometrial tissue from mares at different disease stages (Kenney and Doig categories I–III) across the estrous cycle, quantifying LPA and its four known receptors alongside measuring secretion of connective tissue growth factor (CTGF) and prostaglandins. In healthy (category I) endometrium, LPA concentrations were significantly higher during the luteal phase than the follicular phase; critically, LPA stimulated PGE2 secretion across both cycle phases in normal tissue, but this response became dysregulated in endometrosis, with altered effects on both CTGF and the PGE2/PGF2α ratio depending on disease severity. These findings suggest that endometrosis disrupts LPA signalling pathways that normally regulate the inflammatory and fibrotic balance essential for fertility, potentially compromising embryo implantation and placental development. Clinicians should recognise that endometrotic changes extend beyond structural fibrosis to encompass fundamental alterations in endocrine and paracrine signalling; future diagnostic and therapeutic approaches may benefit from targeting these disrupted signalling cascades rather than fibrosis alone.
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Practical Takeaways
- •Endometrosis disrupts normal endometrial signalling pathways involving LPA and prostaglandins, potentially compromising fertility and early pregnancy establishment in affected mares
- •The altered LPA-mediated response in fibrotic endometrium suggests endometrosis creates a pro-inflammatory microenvironment that may be therapeutically targetable
- •Understanding these molecular changes provides potential biomarkers for assessing endometrial quality and predicting reproductive outcomes in mares with endometrosis
Key Findings
- •Endometrial LPA concentration was significantly higher in mid-luteal phase compared to follicular phase in healthy endometrium (P<0.01)
- •LPA receptor (LPAR1-4) protein abundance and endometrial LPA concentrations were altered across different endometrosis grades during the follicular phase (P<0.05)
- •LPA stimulation increased PGE2 secretion from healthy endometrium in both estrous cycle phases (P<0.05)
- •LPA effects on CTGF and PGF2α secretion were stage-dependent, varying significantly with severity of endometrosis (P<0.05)