Endocrine Abstracts

Endometriosis is a hormone-dependent disorder, characterised by growth of endometrial tissue outside the uterus. It has been reported that 30–40% of women with infertility have endometriosis. Transformation of human endometrial stromal fibroblasts (hESC) (termed decidualisation) is accompanied by increased steroid synthesis and is fundamental to the establishment of a receptive endometrial microenvironment, which can support and maintain pregnancy. Evidence suggests that women with endometriosis have an impaired decidualisation response. In the current study, we have compared the decidualisation response of women with and without endometriosis, examined the temporal expression of decidualisation factors and steroidogenic enzymes and explored the impact of steroid receptor ligands. Primary hESCs from women with and without endometriosis were recovered during the proliferative phase of the menstrual cycle and incubated with progesterone and cAMP to model decidualisation in vitro. Co-treatment with androgen receptor ligands (DHT, flutamide) was performed. Culture media, RNA and protein samples were recovered on days 1, 2, 4 and 8 of treatment. Expression of decidualisation markers (IGFBP1, PRL, FOXO1) and steroidogenic enzymes (AKRIC3, SRD5A1) was determined and concentrations of secreted IGFBP1, PRL and DHT measured by ELISA. Results revealed time-dependent changes in gene and protein expression, with evidence that local (intracrine) biosynthesis of androgens may a role in regulation of decidualisation. Decidualisation of hESCs from women with endometriosis was characterised by different patterns of expression of the key androgen-metabolising enzymes AKR1C3 and SRD5A1 compared to hESC from women without endometriosis. Flutamide appeared to differentially affect decidualisation of hESCs from women with and without endometriosis.

Presenting Author: Ioannis Simitsidellis, MRC Centre for Inflammation Research, The University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland. Email: [email protected]