Pathogenesis of Endometriosis: New Insights into Prospective Therapies

Abstract

Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2-10% of women experience this condition during reproductive age, 35-50% of whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis and treatment, other than surgical procedures and scans. It is difficult to identify the disease at its onset, unless symptoms such as infertility and/or pain are present. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Endometriosis is characterized by cell proliferation, propagation, evasion of immunosurveillance, and invasive metastasis. This review reports the underlying mechanisms that are individually or collectively responsible for disease establishment and evolution. Treatment of endometriosis mainly involves hormone therapies, which may be undesirable or have their own repercussions. It is therefore important to devise alternative strategies that are both effective and cause fewer side effects. Use of phytochemicals may be one of them. This review focuses on pharmacological inhibitors that can be therapeutically investigated in terms of their effects on signaling pathways and/or mechanisms involved in the pathogenesis of endometriosis.

Keywords: angiogenesis; apoptosis; endometriosis; epithelial–mesenchymal transition; estrogen signaling; inflammation; medical therapy; pathogenesis; pharmacological inhibitors.

Figure 1

Summary of the mechanisms involved in endometriosis initiation and progression. Endometrial tissue/cells are carried by retrograde menstruation to ectopic locations (peritoneum), where high expression of integrins facilitates their implantation. The constant hyperestrogenism observed in endometriosis, followed by enhanced cell proliferation and survival, leads to lesion development and progression. At the same time, accumulating macrophages release a number of inflammatory mediators, thereby triggering the process of EMT, with the subsequent invasion and angiogenesis/neuroangiogenesis leading to lesion growth and the generation of pain symptoms in endometriosis patients.