The Origin and Pathogenesis of Endometriosis

Wang, Yeh; Nicholes, Kristen; Shih, Ie Ming

doi:10.1146/annurev-pathmechdis-012419-032654

Cited by 287 publications

(265 citation statements)

References 133 publications

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“…Although endometriosis is a benign condition a number of parallels can be drawn between the condition and cancer (118). Macrophages are unambiguously at the center of the pathophysiology of both diseases.…”

Section: Macrophages Can Promote Diseasementioning

confidence: 99%

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

2020

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Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting ∼176 million women worldwide. It is associated with chronic pelvic pain, infertility, and fatigue, and has a substantial impact on health-related quality of life. Endometriosis is defined by the growth of endometrial-like tissue outside the uterus, typically on the lining of the pelvic cavity and ovaries (known as "lesions"). Macrophages are complex cells at the center of this enigmatic condition; they are critical for the growth, development, vascularization, and innervation of lesions as well as generation of pain symptoms. In health, tissue-resident macrophages are seeded during early embryonic life are vital for development and homeostasis of tissues. In the adult, under inflammatory challenge, monocytes are recruited from the blood and differentiate into macrophages in tissues where they fulfill functions, such as fighting infection and repairing wounds. The interplay between tissue-resident and recruited macrophages is now at the forefront of macrophage research due to their differential roles in inflammatory disorders. In some cancers, tumor-associated macrophages (TAMs) are comprised of tissue-resident macrophages and recruited inflammatory monocytes that differentiate into macrophages within the tumor. These macrophages of different origins play differential roles in disease progression. Herein, we review the complexities of macrophage dynamics in health and disease and explore the paradigm that under disease-modified conditions, macrophages that normally maintain homeostasis become modified such that they promote disease. We also interrogate the evidence to support the existence of multiple phenotypic populations and origins of macrophages in endometriosis and how this could be exploited for therapy.

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Section: Macrophages Can Promote Diseasementioning

confidence: 99%

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

2020

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“…Endometrial stem cells. The endometrial stem cell implantation theory is an expansion of the retrograde menstruation theory (33). Endometrial epithelial progenitor cells and mesenchymal stem-cell-like cells, together with the menstruation are shed into the peritoneum, where they implant and establish the ectopic lesions.…”

Section: Human Primary Endometrial Epithelial Cells (Eecs) and Endomementioning

confidence: 99%

“…Chicken chorioallantoic membranes (CAMs) and amniotic membranes culture model. In the retrograde menstruation theory, endometrium encounters the peritoneum, implants, invades and forms the ectopic endometrium and endometriotic lesions (33). Therefore, the peritoneum represents the other side of the endometriosis pathogenesis.…”

Section: Human Primary Endometrial Epithelial Cells (Eecs) and Endomementioning

confidence: 99%

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In‑vitro models of human endometriosis (Review)

Fan

2019

Exp Ther Med

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Endometriosis is one of the most common benign gynecological diseases in women of reproductive age worldwide. In past decades, a number of in-vitro models have been used to investigate the pathology and therapeutic methods for the treatment of endometriosis. The current review summarized the majority of currently available in-vitro models, which utilize a variety of cell or tissues types, including endometriotic cell lines, primary endometrial stromal cells, endometrial stem cells, endometrial explants, peritoneal explants and immune cells. These cells or tissues are cultured individually, co-cultured in 2D or 3D systems with various matrices or cultured in chicken chorioallantotic membranes and amniotic membranes culture systems. These models are able to represent one or more aspects of the process of endometriosis. These models are helpful and can be used to investigate the development of endometriosis and the underlying mechanisms of this disorder in detail, and help investigators select appropriate models for their experiments. Recently, the new concept of endometriosis as a fibrotic condition will lead research to investigate the differentiation of myofibroblasts and the development of fibrosis in endometriotic lesions, which will increase the development of novel models that can be used to investigate endometriotic fibrosis. Contents 1. Introduction 2. In-vitro models 3. Discussion In-vitro models of human endometriosis (Review)

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“…In both species cyclical homeostatic regeneration of the endometrial epithelium is expected to be maintained by stem cells. However, the presence and location of such cells has been actively debated for the last several decades (reviewed in Gargett et al, 2016;Wang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

PAX8 expressing epithelial cells are a cancer-prone source of clonal cyclical regeneration of endometrial epithelium

Micheli

Bidarimath

et al. 2019

Preprint

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Humans and mice have cyclical regeneration of the endometrial epithelium. It is expected that such regeneration is ensured by tissue stem cells. However, their location remains debatable. A number of recent studies have suggested the presence of stem cells in the mouse endometrial epithelium. At the same time, it has been reported this tissue can be regenerated by stem cells of stromal/mesenchymal or bone marrow cell origin. Here we show that cells expressing transcription factor PAX8 are the main contributor to the homeostatic regeneration of endometrial epithelium. In the uterus, based on a single-cell transcriptome and immunostaining analyses, PAX8 expression is limited to the endometrial epithelium. According to lineage tracing, PAX8 positive (PAX8+) epithelial cells are responsible for long-term maintenance of the epithelium. Furthermore, multicolor tracing shows that individual glands are formed by clonal expansion of cells labeling both glandular and luminal epithelial components. Inactivation of tumor suppressor genes Trp53 and Rb1 in PAX8+ cells but not FOXJ1+ cells leads to formation of neoplasms with features of serous endometrial carcinoma, the most aggressive type of human endometrial malignancy. Taken together, our results show that a progeny of single PAX8+ cells represent the main source of cyclical regeneration of the endometrial epithelium.They also provide direct experimental genetic evidence for the key roles of the P53 and RB pathways in the pathogenesis of serous endometrial carcinoma, and suggest that PAX8+ cells represent the cell-of-origin of this neoplasm.

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The Origin and Pathogenesis of Endometriosis

Cited by 287 publications

References 133 publications

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

In‑vitro models of human endometriosis (Review)

PAX8 expressing epithelial cells are a cancer-prone source of clonal cyclical regeneration of endometrial epithelium

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