Tubal origin of ovarian endometriosis

Zeng, Yuan; Wang, Lijie; Wang, Yiying; Zhang, Tingguo; Li, L i; Cragun, Janiel M.; Chambers, Setsuko K.; Kong, Beihua; Zheng, Wenxin

doi:10.1038/modpathol.2013.245

Cited by 29 publications

(15 citation statements)

References 46 publications

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“…Aside from hepatic tumors, there is little work on the role of FMO3 in other tissues or tumors. Curiously, it is expressed in the Fallopian tubal epithelium [ 39 ]. One might speculate that FMO3 upregulation might be associated with resistance to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

et al. 2016

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Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ∼80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

et al. 2016

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“…Up to 90% of women of reproductive age exhibit retrograde menstruation, whereas only 6–10% of these women develop endometriosis. 20 This indicates that a microenvironment of immune tolerance is formed within the ectopic lesion in patients with endometriosis, where the function of menstrual debris clearance by the local immune responses is ineffectively. 21 …”

Section: Discussionmentioning

confidence: 99%

1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

et al. 2016

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Foxp3+ regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of Treg cells, mainly IL-10+ Treg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated Treg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of Treg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for Treg differentiation in the ectopic lesion, especially that for CD4high Treg. Therefore, MRC2-silenced ESCs-educated Treg manifested a stronger suppressive function in vitro. Consistently, the percentage of Treg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of Treg and is involved in the development of endometriosis. Thus, blockage of IDO1 in the ectopic lesion, which does not influence physiological functions of estrogen, may be considered a potential therapy for endometriosis.

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“…Inflammation, a hallmark of endometriosis, is induced by tubal endometriosis and may contribute to FT dysfunction and disease progression [ 17 , 18 ]. As well as contributing to other endometriosis subtypes, desquamation of the endosalpinx may play a pivotal role in ovarian endometrioma formation, which are known precursors of malignant neoplasms [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications

Hill

Fakhreldin

Maclean

et al. 2020

JCM

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Endometriosis is a common, oestrogen driven chronic condition, where endometrium-like epithelial and stromal cells exist in ectopic sites. At present, no curative treatments are available and the existing evidence for disease progression is conflicting. The pathogenesis is still unknown and evidently complex, as mechanisms of initiation may depend on the anatomical distribution of endometriotic lesions. However, amongst the numerous theories and plethora of mechanisms, contributions of the fallopian tubes (FT) to endometriosis are rarely discussed. The FT are implicated in all endometriosis associated symptomatology and clinical consequences; they may contribute to the origin of endometriotic tissue, determine the sites for ectopic lesion establishment and act as conduits for the spread of proinflammatory media. Here, we examine the available evidence for the contribution of the human FT to the origin, pathogenesis and symptoms/clinical consequences of endometriosis. We also examine the broader topic linking endometriosis and the FT epithelium to the genesis of ovarian epithelial cancers. Further studies elucidating the distinct functional and phenotypical characteristics of FT mucosa may allow the development of novel treatment strategies for endometriosis that are potentially curative.

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Tubal origin of ovarian endometriosis

Cited by 29 publications

References 46 publications

Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications

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