The endometrial-myometrial interface (EMI) in the aetiopathophysiology of adenomyosis uteri

Adenomyosis is a uterine disease where ectopic, non-neoplastic endometrium is histologically observed within the myometrium. The research presented herein examines the hypothesis that uterine adenomyosis is caused by abnormal behaviour of the cells at the endometrial-myometrial interface (EMI) through the actions of nerve growth factors (NGF), their receptors, the caveolin proteins and wnt signalling pathways during estradiol (E2) or tamoxifen (TMX) stimulation. In a 3-dimensional coculture model, the invasion depth of endometrial stromal cells from affected uteri was greater than that of unaffected uteri. Furthermore, invasion depth of unaffected and affected stromal cells increased by an average of 41.3% and 64.6%, respectively in the presence of E2 and 73.3% and 73.5%, respectively in the presence of TMX, indicating an inherent predisposition of the stromal cell for myometrial invasion and the enhancing effects of both E2 and TMX. Immunohistochemical analysis of NGF expression indicated a significant 2-4 fold increase in adenomyosis with the transcript level (measured by qRT-PCR) showing decreased expression in normal myocytes (0.72 fold) in response to E2 and increased expression in both normal (1.08 fold) ... (continues)