The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights

• Published in: International journal of molecular sciences 2019-11, Vol.20 (22), p.5615
• Main Authors: Laganà, Antonio Simone, Garzon, Simone, Götte, Martin, Viganò, Paola, Franchi, Massimo, Ghezzi, Fabio, Martin, Dan C
• Format: Article
• Language: English
• Subjects: Acids; Angiogenesis; Apoptosis; Cell cycle; Endometriosis; Endometriosis - genetics; Endometriosis - pathology; Endometrium; Endometrium - metabolism; Endometrium - pathology; Epigenesis, Genetic; Female; Gynecology; Humans; MicroRNAs; Obstetrics; Ovarian cancer; Pathogenesis; Review; Stem Cells - metabolism; Stem Cells - pathology; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20225615

The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term "Endometriosis" (ID:D004715) with "Etiology" (ID:Q000209), "Immunology" (ID:Q000276), "Genetics" (ID:D005823) and "Epigenesis, Genetic" (ID:D044127). Endometriosis may origin from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.