Unveiling the Plasma and Tissue Lipid Profiles of a Murine Model of Endometriosis

Disha Shah

Endometriosis is a chronic, benign disease, where the gold standard for diagnosis involves surgery, however there is a multi-year delay to diagnosis and treatment. Despite the urgent need, little progress has been made in discovery and validation of minimally-invasive diagnostic biomarkers for endometriosis. In this regard, animal models may contribute to the investigation of endometriosis pathogenesis and biomarker discovery. Using a preclinical murine model of endometriosis, the first aim of this project was to utilise mass spectrometry (MS) to investigate and compare lipidomic profiles of plasma from endometriosis and sham mice. The second aim was to employ MS imaging to spatially characterise endometriotic lesions from mice, and to identify if lipids and metabolites found in lesions correlate with those found in plasma. Comparative analysis of plasma lipids found 57 features to be associated with endometriosis. These included a range of fatty acids, di- and triacylglycerols, lysophospholipids, phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, and sphingolipids. MSI analysis identified 32 discriminatory features between endometriotic lesions and fat tissues. The main lipids identified included phosphatidylcholines and phosphatidylethanolamines. One lipid, PC 34:2, was conserved in both plasma and endometriotic lesions from endometriosis mice, making it a potential candidate as a minimally-invasive diagnostic biomarkers of endometriosis. This investigation demonstrated the utility and limitations of murine endometriosis models and MS in identification of aberrant metabolic profiles between cases and controls, providing information on how lipids and metabolites may be contributing to disease pathophysiology through the biological pathways identified. It also highlighted the potential of MSI for direct characterisation of endometrial tissue and endometriotic lesions. While a biomarker candidate was identified in this study, further research with larger cohort sizes and validation in humans with endometriosis is warranted. The information generated provides information on how lipids and metabolites may be contributing to disease pathophysiology.

Unveiling the Plasma and Tissue Lipid Profiles of a Murine Model of Endometriosis

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