In Search of Pathogenic Mechanisms in Endometriosis: The Challenge for Molecular Cell Biology
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This review discusses the cellular basis of endometriosis lesion formation, focusing on the potential role of a plastic founder cell population with self-renewal capacity that responds to host environment stimuli.
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Abstract
Endometriosis, defined histologically as the presence of endometrium-like glands and stroma outside the uterus, is a chronic, invasive and metastasising disease. It shares features with malignant tumours (invasion and metastasis) but is not neoplastic. Despite the fact that endometriosis is one of the most frequent gynaecological diseases, it is under researched, puzzling and highly debated. The aetiology and pathogenesis is little understood although it is agreed that implantation, at least in many cases, is responsible for endometriosis. This theory advocates retrograde menstruation as the underlying phenomenon, where cells of the menstrual efflux provide the cellular source for endometriotic lesion formation. Causative therapy and non-invasive diagnostics of endometriosis do not exist. Thus, there is a substantial but unmet need for molecular and cellular research to unravel the pathogenic mechanisms of endometriosis as a basis for developing novel diagnostic and therapeutic concepts. In this review, we specifically focus on the cellular basis of lesion formation, the possible modulation of this by cytokines and other factors and the characteristics of endometriotic cells in terms of invasion and metastasis. Considering available experimental information, we concentrate on arguments and ideas in favour of an endometriotic founder cell population exhibiting substantial plasticity for differentiation and self-renewal. Perhaps present in the menstrual efflux or arising by metaplasia (a complementary theory to implantation), this cell type might respond to stimuli present in the ectopic host environment and establish the endometriotic phenotype.
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Cited by (45)
- The Pathological Role of miRNAs in Endometriosis 2023
- Endometriosis - Recent Advances, New Perspectives and Treatments 2021
- Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis 2021
- Potential Therapeutic Options and Perspectives for Alleviation of Endometrial Estrogen Dominance and Progesterone Resistance in Endometriosis 2021
- Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity 2020
- Establishment of endometriotic models: the past and future 2020
- Molecular Mechanisms Underlying Adolescent Endometriosis and Advancements in Medical Management 2020
- Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: results from the EndEA study 2020
- Identification of key genes and pathways in endometriosis by integrated expression profiles analysis 2020
- Progesterone Resistance and Adult Stem Cells’ Genomic and Epigenetic Changes in the Puzzle of Endometriosis 2019
- CTHRC1 overexpression promotes ectopic endometrial stromal cell proliferation, migration and invasion via activation of the Wnt/β-catenin pathway 2019
- Angiogenic properties of endometrial mesenchymal stromal cells in endothelial co-culture: an in vitro model of endometriosis 2017
- Molecular and Cellular Pathogenesis of Endometriosis 2017
- The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding 2016
- Cells with “Stemness”: Seeds for endometriosis? 2016
- Spatial and temporal characterization of endometrial mesenchymal stem-like cells activity during the menstrual cycle 2016
- Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis 2014
- Effect of LIM kinase 1 overexpression on behaviour of endometriosis-derived stromal cells 2014
- Endometrial Adult/Progenitor Stem Cells: Pathogenetic Theory and New Antiangiogenic Approach for Endometriosis Therapy 2013
- Endometrial regeneration and endometrial stem/progenitor cells 2012
- Histone deacetylase inhibitors as therapeutics for endometriosis 2012
- The Epigenetics of Endometriosis 2012
- Stem Cells in Endometriosis 2011
- Pathogenesis: Epigenetics 2011
- Interleukin-1β induces cyclooxygenase-2 expression and promotes the invasive ability of human mesenchymal stem cells derived from ovarian endometrioma 2011
- In vitro model of stromal and epithelial immortalized endometriotic cells 2011
- Expression of tyrosine kinase receptor B in eutopic endometrium of women with adenomyosis 2010
- Resistin Concentration is Increased in the Peritoneal Fluid of Women with Endometriosis 2010
- Expressão qualitativa de genes relacionados à atividade de células tronco em mulheres inférteis com endometriose peritoneal 2010
- Adult stem cells in the endometrium 2010
- The Endometrium: A Novel Source of Adult Stem/Progenitor Cells 2009
- Induction of peritoneal endometriosis in nude mice with use of human immortalized endometriosis epithelial and stromal cells: a potential experimental tool to study molecular pathogenesis of endometriosis in humans 2008
- Regulation and activation of ezrin protein in endometriosis 2008
- <i>Endometriosis and Tissue Factor</i> 2008
- Hormone and growth factor signaling in endometrial renewal: Role of stem/progenitor cells 2008
- Ultrastructure of Ectopic Peritoneal Lesions From Women With Endometriosis, Including Observations on the Contribution of Coelomic Mesothelium 2008
- Trichostatin A, a Histone Deacetylase Inhibitor, Attenuates Invasiveness and Reactivates E-Cadherin Expression in Immortalized Endometriotic Cells 2007
- Expression of p63 Differs in Peritoneal Endometriosis, Endometriomas, Adenomyosis, Rectovaginal Septum Endometriosis, and Abdominal Wall Endometriosis 2007
- Prevalence and distribution of adnexal findings suggesting endometriosis in patients with MR diagnosis of adenomyosis 2006
- Nuclear Factor-κB (NF-κB): An Unsuspected Major Culprit in the Pathogenesis of Endometriosis That Is Still at Large? 2006
- Uterine stem cells: What is the evidence? 2006
- Noninvasive diagnosis of endometriosis: the role of imaging and markers 2003
- Inverse correlation between peritoneal fluid leptin concentrations and the extent of endometriosis 2003
- Increased levels of interleukin-15 in the peritoneal fluid of women with endometriosis: inverse correlation with stage and depth of invasion 2003
- Aromatase und Cyclooxygenase-2 – neue Ansätze in der Endometriosetherapie? 2002
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