Commentary on major developments in the pathophysiology of endometriosis

Commentary on major developments in the pathophysiology of endometriosis

Hypoxia-induced autophagy and epithelial to mesenchymal transition seem to be the key factors in invasive endometriosis

Key Points


  • Endometriosis is an estrogen-dependent disease defined by growth of endometrial glands and stroma outside the uterine cavity leading to pelvic pain and infertility. Endometriosis is estimated to affect up to 10% of women or 176 million women world wide.

  • Recent research has revealed that signaling pathways are central to the pathophysiology of endometriosis, however the underlying mechanisms for progression and infiltration seem to be different than the implantation phase properties


  • While endometriosis remains a complex disease of unknown cause, results of recent studies provide us a clearer picture of the pathophysiology with several molecular aspects revealed more precisely with activation of autophagy cascade being crucial in established lesions

What's done here:

  • In this commentary, recently recognized putative molecular factors related to the initiation, progression and infiltrative properties of endometriotic lesions are outlined





Lay Summary

This commentary article by Dr. Warren G. Foster, from MacMaster University, Canada that appeared at Biology of Reproduction, is highly valuable for its leading role in endometriosis research.

Although endometriosis is a common disease affecting up to 10% of women, frequently causing pelvic pain and infertility its etiology remains a myth. Basically, it is an estrogen-dependent disease having endometrial tissue outside the uterine cavity. While retrograde menstruation is the most widely accepted theory of causation, regurgitation of menstrual effluent through the fallopian tubes occurs in approximately 90% of women. 

Recent research revealed that signaling pathways are central to the pathophysiology of endometriosis with special emphasis on dysregulation of aromatase expression leading to the de novo production of estrogens. Endometriotic implants overexpress estrogen receptor β (EsR2) leading to transcriptional repression of estrogen receptor α (EsR1) and progesterone receptor expression. Overexpression of EsR2 modulates tumor necrosis factor-α (TNF-α) mediated apoptosis and enhanced recruitment of inflammatory mediators, i.e. evasion from apoptosis. 

However, contrary to the established endometriotic implants, newly forming implants are estrogen independent and the initial steps in endometriotic implant development seem to be dependent on immune system modulation. Dysregulation of miR-451 expression is also another emerging point in this regard.

Akin to cancer, shed endometrial cells survive under hypoxic conditions, attach to distant anatomical sites, undergo epithelial to mesenchymal transition (EMT), and develop an invasive phenotype through upregulation of hypoxia-inducible factor-1α (HIF-1α) expression and activate the self-digestion pathway (autophagy). Future studies are needed to clarify the impact of the interaction between cells in the implantation site and endometrial cells since various endometrial implants are thought to be different functionally.

Initiation of lesions is likely an estrogen-independent process and recent findings suggest that hypoxia-induced activation of the autophagy cascade is central to EMT and invasive characteristic of cells in endometriotic implants.

Research Source:

autophagy invasive EsR2 miR-451 HIF-1alpha EMT commentary


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