ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2016) 44 OC6.6 | DOI: 10.1530/endoabs.44.OC6.6

Defining the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis

Syed F Ahmad1, Roderick N Carter3, Frances Collins2, Erin Greaves1, Nicholas M Morton3, Philippa TK Saunders2 & Andrew W Horne1

1MRC Centre for Reproductive Health, Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, UK; 2MRC Centre for Inflammation Research, Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, UK; 3Centre for Cardiovascular Science, Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.

Endometriosis is a chronic oestrogen-dependent incurable inflammatory disorder, defined by the presence of endometrial-like tissue outside the uterine cavity that affects 6–10% of women of reproductive age. It is associated with debilitating pelvic pain and subfertility with a significant impact on quality of life and estimated annual costs to the UK of £11.7 billion. Recent findings from our laboratory have shown that there is a shift in cell metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis in the peritoneal microenvironment of women with endometriosis compared to women without disease, a phenomenon known as the ‘Warburg effect’. Similar changes in metabolism in tumour cells have been shown to promote cell invasion, angiogenesis and immune suppression, all of which are important steps in the development of endometriosis. The objective of this current work is to gain a better understanding of the bio-energetic phenotype of the peritoneal mesothelial cells from the women with endometriosis. Human peritoneal mesothelial cells (HPMC) were collected with informed consent by peritoneal brushing from women with and without endometriosis (n=6). The Seahorse XF glycolytic stress assay was used to define the metabolic phenotypes of endometriosis-associated peritoneal mesothelial cells by simultaneously measuring glycolysis (Extra Cellular Acidification Rates) and mitochondrial respiration (Oxygen Consumption Rates) providing quantifiable metabolic data. HPMCs from women with endometriosis show higher levels of glycolysis and lower mitochondrial respiration compared to women without disease. Specifically, HPMCs from women with endometriosis show a significant increase in glycolysis (p<0.01) and glycolytic capacity (p<0.01) and a significant reduction in ATP production due to mitochondrial respiration (p<0.001). These data indicate that HPMCs from women with endometriosis primarily utilize aerobic glycolysis, which in turn results in increased lactate to support the growth and establishment of endometriosis. Targeting lactate metabolism may offer potential as novel therapeutics for endometriosis.

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