The Origin and Pathogenesis of Endometriosis

Recent molecular genetic findings on endometriosis and normal endometrium suggest a modified model in which circulating epithelial progenitor or stem cells intended to regenerate uterine endometrium after menstruation may become overreactive and trapped outside the uterus. These trapped epithelium-c...

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Bibliographic Details
Published in:Annual review of pathology Vol. 15; p. 71
Main Authors: Wang, Yeh, Nicholes, Kristen, Shih, Ie-Ming
Format: Journal Article
Language:English
Published: United States 24.01.2020
Subjects:
Endometriosis - etiology
Endometriosis - pathology
Endometrium - embryology
Endometrium - physiology
Estrogen Receptor beta - genetics
Estrogen Receptor beta - metabolism
Female
Humans
Menstruation - physiology
Ovarian Neoplasms - etiology
Ovarian Neoplasms - pathology
Receptors, Progesterone - genetics
Receptors, Progesterone - metabolism
Signal Transduction - genetics
Stromal Cells - physiology
Uterus - pathology
Uterus - physiology
genetic and epigenetic alterations
stem cell
ovarian cancer
endocrine dysregulation
endometriosis
chronic inflammation
immune dysregulation
ISSN:1553-4014, 1553-4014
Online Access:Get more information
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Summary:Recent molecular genetic findings on endometriosis and normal endometrium suggest a modified model in which circulating epithelial progenitor or stem cells intended to regenerate uterine endometrium after menstruation may become overreactive and trapped outside the uterus. These trapped epithelium-committed progenitor cells form nascent glands through clonal expansion and recruit polyclonal stromal cells, leading to the establishment of deep infiltrating endometriosis. Once formed, the ectopic tissue becomes subject to immune surveillance, resulting in chronic inflammation. The inflammatory response orchestrated by nuclear factor-κB signaling is exacerbated by aberrations in the estrogen receptor-β and progesterone receptor pathways, which are also affected by local inflammation, forming a dysregulated inflammation-hormonal loop. Glandular epithelium within endometriotic tissue harbors cancer-associated mutations that are frequently detected in endometriosis-related ovarian cancers. In this review, we summarize recent advances that have illuminated the origin and pathogenesis of endometriosis and have provided new avenues for research that promise to improve the early diagnosis and management of endometriosis.
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ISSN:1553-4014
1553-4014
DOI:10.1146/annurev-pathmechdis-012419-032654