Endocrine Abstracts

Endometriosis is a chronic hormone-dependent disorder, characterised by growth of ‘ectopic’ endometrial tissue outside the uterus. It has been reported that 30–40% of women who are sub/infertile have endometriosis. Infertility in women with severe endometriosis may be the result of either scarring or pelvic distortion, but in women with mild/moderate disease it is believed subfertility may result from disturbances in endometrial tissue function. Transformation of human endometrial stromal fibroblasts (hESC) into specialised secretory cells (decidualisation) 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, HOXA10, FOXO1) and steroidogenic enzymes (AKRIC3, SRD5A1) was determined and concentrations of secreted IGFBP1, PRL and DHT measured by ELISA.

Results revealed striking and consistent time-dependent changes in gene and protein expression, with evidence that local (intracrine) biosynthesis of androgens plays a role in regulation of decidualisation. In contrast to those of control cells, responses of hESCs from women with endometriosis were not uniform, with several exhibiting rapid/transient responses consistent with blunted decidualisation. In conclusion, hESC from women with endometriosis appear to retain a ‘memory’ of altered in vivo responsiveness providing a platform for development of novel therapies.