Towards understanding mare endometrosis: ex vivo study on the role of relaxin

CONTEXT: Mare endometrosis remains a poorly understood pathological process. AIMS: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H), or treated with vehicle (Hveh), and tissues with endometrosis that were left untreated (E), treated with vehicle (Eveh), and treated with RLX (10, 25, 50 nM; ER) were used for an ex vivo system for 72 h. METHODS: Tissue histological examination, and immunoenzymatic measurement of the concentrations of transforming growth factor β (TGF-β), interleukins (IL-6 and IL-8), and progesterone were performed. Western blotting was used to study the abundance of the following proteins involved in cellular processes, signaling, and interactions: N-cadherin, cortactin, Wnt/β-catenin signaling with kinases: glycogen synthase kinase-3β (GSK-3β), protein kinase B (AKT), metalloproteinases: MMP9, MMP2, and cyclins: D1, D3. KEY RESULTS: RLX (50 nM) decreased the concentration of TGF-β, increased concentrations of IL-6 and IL-8, and decreased the concentration of progesterone, without histological alterations of the treated tissues. Interactions of RLX with proteins showed changes in protein abundance, as follows: N-cadherin increased, cortactin increased, β-catenin, GSK-3β and AKT showed an increase of phosphorylation, MMP2 and MMP9 increased, and cyclin D3 increased in ER versus E. CONCLUSIONS: Results indicated that RLX exerted both anti-/pro-inflammatory as well as anti-/pro-fibrotic effects depending on interacting cytokine/protein. IMPLICATIONS: In equine breeding, the application of RLX with marker protein antagonists/agonists may be promising in endometrial fibrosis treatment.