Endocrine Abstracts

Endometriosis is a chronic incurable hormone dependent condition characterized by growth of endometrial tissue in sites outside the uterus: 30–40% of women with endometriosis have sub/infertility however the underlying cause is unknown. We have previously demonstrated that steroid-induced differentiation of endometrial stromal cells (hESC) (decidualisation) is associated with increased expression of metabolic genes that are thought to be essential to support the implanting blastocyst. Disordered glucose metabolism by hESC has been implicated as a cause of subfertility. The aim of this study was to compare the metabolic phenotype of hESC from women with and without endometriosis so as to inform our understanding of the mechanisms underpinning infertility in this patient group. Primary hESC from the proliferative phase of the cycle were isolated from endometrial biopsies collected from women with endometriosis (n=8) and women with no evidence of endometriosis (n=6). Decidualisation was induced in vitro (progesterone and cAMP) and metabolic analysis performed on days 1, 2, 4 and 8 using the Seahorse bioanalyser. RNA was isolated from cells to examine expression of genes involved in metabolism by qRT-PCR: secretion of decidualisation-associated proteins (e.g. IGFBP1) were measured in media by Elisa. Seahorse analysis revealed a significant shift towards increased glycolysis in decidualised hESC compared to undecidualised cells (as determined by extracellular acidification rate, ECAR) with a corresponding drop in glycolytic reserve. Cellular oxygen consumption rate (OCAR) revealed a significant decrease in ATP production and a significant decrease in coupling efficiency in primary hESC from women with endometriosis compared with controls. Decidualisation was associated with a significant increase in IGFBP and PPARGC1A (coordinates gene expression regulating mitochondrial biogenesis) and a decrease in PCK2 (implicated in metabolic reprogramming). The results demonstrate a shift towards a ‘Warburg’ like phenotype in hESC during decidualisation that appears altered in women with endometriosis.