Mare endometrosis induces endometrial proteome changes

Endometrosis, characterized by excessive endometrial fibrosis, is a major reproductive disorder that impairs fertility and remains a significant challenge in equine breeding. The molecular mechanisms underlying equine endometrosis are not fully understood. This study investigated endometrial proteomic changes induced by endometrosis to identify the biological processes (BP) and pathways involved. Cyclic mares' endometrial biopsies were categorized as category IIA (n = 5) or category IIB (n = 5), according to Kenney and Doig's classification. LC-MS/MS assessed the endometrial proteome, and differentially abundant proteins (DAPs) were identified using p < 0.05 and |log2FC| ≥ 1. A total of 100 DAPs were identified in category IIB endometria, compared to category IIA, mainly enriched in BP and pathways related to cell growth, structural organization, apoptotic processes, immune response/inflammation, and oxidative stress. The enrichment of the upregulated proteins in IIB endometria, in BP terms related to oxidative stress response and regulation of epithelial-mesenchymal transition, also suggests the involvement of these processes in endometrosis development and progression. Accordingly, endometrosis was associated with a higher abundance of proteins related to oxidative stress, including peroxidasin and glutathione S-transferases, as well as proteins involved in fibrotic and inflammatory processes, including CD5 molecule-like protein, serpin proteins, and histone H2A. The Western blot analysis of Histone H2A, a core component of chromatin structure associated with chromatin remodelling and gene transcription, further confirmed its higher abundance in category IIB endometria compared to IIA. Overall, this study identified proteins potentially involved in endometrosis development and progression.