A comprehensive review on the etiopathogenesis of endometriosis

A single etiopathogenetic explanatory model is not sufficient for endometriosis

Key Points

Importance:

• The pathogenesis of endometriosis is a complex multifactorial process leading to the development of a heterogeneous disease.

What's done here:

• Publications retrieved from computerized medical databases using the headings  “Endometriosis”  with “Etiology”, “Immunology”, “Genetics” and “Epigenesis, Genetic” were analyzed.
• The subjects reviewed and summarized are:
  
  • Theories on the origin of endometriosis (in situ theory versus transplantation theory)
  • Behind the origin of endometriosis (comprehensive models, the role of hormones, peritoneal microenvironment-immune surveillance, apoptosis defects, cell matrix/cell adhesion, extracellular matrix remodeling and matrix proteinases, angiogenesis, endometrial stem cells)
  • Genetics of endometriosis (Candidate gene analyses, linkage and association studies, genome-wide association studies)
  • Epigenetics (both eutopic endometrium and endometriosis)

Key results: 

• Endometriosis may origin from Müllerian or non-Müllerian stem cells.
• The presence of such cells in the peritoneum and the development of endometriosis is a complex process.
• There is a large number of interconnected factors, both inherited and exogenous. 
• Genetic predisposition is related to the mutual action of several genes with limited influence.
• The epigenetic mechanisms also control many of the processes involved in the immunologic and biological aberrations. 
• The heterogeneity of endometriosis and the different contexts in which it develops suggest that it has complex pathogenesis.

Lay Summary

Endometriosis, being a heterogeneous disease has a highly complex etiopathogenesis. 

A multicenter comprehensive review on this important subject from Italy, Germany, and the USA by Lagana and associates, was recently published in the "International Journal of Molecular Sciences" an open-access journal. Computerized databases were used to retrieve publications using the Medical Subject Headings (MeSH)  “Endometriosis”  with “Etiology”, “Immunology”  “Genetics”  and “Epigenesis, Genetic”. 

Available scientific evidence reveals that endometriosis is not just simply a transplanted normal endometrium. Numerous differences in hormone receptor levels, histological, morphological, and biological features were reported when comparing endometriosis with eutopic endometrium, with only limited similarities. Further observations suggest that endometriosis may originate from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The endometrial stem cells may regenerate cyclically along with dysregulated hormonal pathways.

The presence of such stem cells and the development of endometriosis is a complicated pathway with a large number of factors both inherited and with limited influence, epigenetic mechanisms controlling many of the steps involved in the immunologic aberrations.

The process is variable and can lead to the development of endometriosis through progressive alterations to the physiological processes of the endometrium.

The authors conclude “The etiopathogenesis of endometriosis is a multifactorial process that leads to the development of an extremely heterogeneous disease characterized by the variable acquisition and loss of cellular functions. The heterogeneity of endometriosis and the different contexts in which it develops suggests that a single etiopathogenetic explanatory model is not sufficient".

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/31717614