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Review
. 2019 Nov 10;20(22):5615.
doi: 10.3390/ijms20225615.

The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights

Antonio Simone Laganà  1 , Simone Garzon  1 , Martin Götte  2 , Paola Viganò  3 , Massimo Franchi  4 , Fabio Ghezzi  1 , Dan C Martin  5   6
Affiliations
Review

The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights

Antonio Simone Laganà et al. Int J Mol Sci. .

Abstract

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.

Keywords: endometriosis; epigenetics; genetics; immunology; pathogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of the mechanisms underlining the key role of estrogens in the pathogenesis of endometriosis. Tissue injury and repair (TIAR); Tumor necrosis factor (TNF); Interleukins (IL); Vascular endothelial growth factor (VEGF); Antiapoptotic protein B cell lymphoma 2 (Bcl-2); 17β-hydroxysteroid dehydrogenase (17β-HSD).
Figure 2
Figure 2
Immunoescaping mechanisms involved in the etiopathogenesis of endometriosis. Human leukocyte antigen class I (HLA-1); Intercellular adhesion molecule-1 (sICAM-1); Natural killer (NK); Cyclo-oxygenase type 2 (COX-2); Interleukins (IL); Tumor necrosis factor (TNF); Vascular endothelial growth factor (VEGF); Antiapoptotic protein B cell lymphoma 2 (Bcl-2); Interferon (INF); transforming growth factor-β (TGF-β).
Figure 3
Figure 3
Epigenetic mechanisms of hypermethylation and hypomethylation involved in the etiopathogenesis of endometriosis. Hypoxia and inflammation regulate DNA methylation through microRNAs (miRNA), and genes coding for three DNA methyltransferases (DNMT) were reported overexpressed in endometriosis. microRNAs (miRNA); DNA methyltransferases (DNMT); Homeobox A transcription factor (HOXA10); Progesterone receptor B (PR-B); 17β-hydroxysteroid dehydrogenase (17β-HSD); Steroidogenic factor-1 (SF-1); Estrogen receptor β (ER-β); Cyclo-oxygenase type 2 (COX-2); Prostaglandin E2 (P-E2); Estrogen (E); Progesterone (P).
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References

    1. Vercellini P., Viganò P., Somigliana E., Fedele L. Endometriosis: Pathogenesis and treatment. Nat. Rev. Endocrinol. 2014;10:261–275. doi: 10.1038/nrendo.2013.255. - DOI - PubMed
    1. Garai J., Molnar V., Varga T., Koppan M., Torok A., Bodis J. Endometriosis: Harmful survival of an ectopic tissue. Front. Biosci. J. Virtual Libr. 2006;11:595–619. doi: 10.2741/1821. - DOI - PubMed
    1. Matalliotakis M., Zervou M.I., Matalliotaki C., Rahmioglu N., Koumantakis G., Kalogiannidis I., Prapas I., Zondervan K., Spandidos D.A., Matalliotakis I., et al. The role of gene polymorphisms in endometriosis. Mol. Med. Rep. 2017;16:5881–5886. doi: 10.3892/mmr.2017.7398. - DOI - PMC - PubMed
    1. Hsiao K., Wu M., Tsai S. Epigenetic regulation of the pathological process in endometriosis. Reprod. Med. Biol. 2017;16:314–319. doi: 10.1002/rmb2.12047. - DOI - PMC - PubMed
    1. Clement P.B. The pathology of endometriosis: A survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv. Anat. Pathol. 2007;14:241–260. doi: 10.1097/PAP.0b013e3180ca7d7b. - DOI - PubMed