TY - JOUR
T1 - The Origin and Pathogenesis of Endometriosis
AU - Wang, Yeh
AU - Nicholes, Kristen
AU - Shih, Ie Ming
N1 - Funding Information:
This review was supported by a grant from the US National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD096147) and the RichardW. TeLinde Gynecologic Pathology Research Program.
Publisher Copyright:
© 2020 Annual Reviews Inc.. All rights reserved.
PY - 2020/1/24
Y1 - 2020/1/24
N2 - 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- beta 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.
AB - 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- beta 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.
KW - endometriosis, ovarian cancer, stem cell, genetic and epigenetic alterations, chronic inflammation, immune dysregulation, endocrine dysregulation
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U2 - 10.1146/annurev-pathmechdis-012419-032654
DO - 10.1146/annurev-pathmechdis-012419-032654
M3 - Review article
C2 - 31479615
AN - SCOPUS:85075715670
VL - 15
SP - 71
EP - 95
JO - Annual Review of Pathology: Mechanisms of Disease
JF - Annual Review of Pathology: Mechanisms of Disease
SN - 1553-4006
ER -