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Objective To define altered gene expression networks in endometriosis. Design Experiments using endometriotic tissues and primary cells. Setting Division of Reproductive Biology Research, Northwestern University. Patient(s) Premenopausal women. Intervention(s) Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients). Main Outcomes Measure(s) Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis. Result(s) Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis. Conclusion(s) The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions.

Objective To non-invasively characterize ectopic uterine tissue (EUT) development in a modified autologous rat surgical model of endometriosis using magnetic resonance imaging (MRI). Design Investigational MRI study. Setting A pharmaceutical company. Animal(s) Female Sprague Dawley rats. Intervention(s) Uterine tissue was autotransplanted on the right peritoneal wall of rats. Rats were serially imaged after surgery and after endogenous hormone suppression, hormone supplementation, or ovariectomy. In addition, an MRI contrast agent was administered to examine EUT perfusion characteristics. Main Outcome Measure(s) Changes in transplanted EUT volume and perfusion were monitored using MRI. Result(s) The EUT growth could be readily monitored non-invasively by MRI. Although EUT growth was rapid during the initial 4 days after surgery, volume stabilized by the third week and maintained for at least 9 weeks after transplantation. The EUT volumes varied with the estrous cycle and were hormonally sensitive to ovariectomy, to Antide (GnRH antagonist), and to Antide followed by 17β-E 2 supplementation. The use of an MRI contrast agent facilitated visualization of EUT wall perfusion. Conclusion(s) MRI allows for noninvasive, dynamic evaluation of transplanted EUT growth in the rat. This reproducible model will allow for performing quantifiable pharmacologic studies in pre-clinical drug discovery for therapies targeting endometriosis.