Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis

Nie, Jichan; Liu, Xishi; Guo, Sun‐Wei

doi:10.1016/j.ajog.2009.11.035

Cited by 68 publications

(72 citation statements)

References 33 publications

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“…Pain Assessment and Serum CA12-5 Levels of Adenomyosis Patients-Pain assessment was performed in 40 adenomyosis patients (these 40 patients fell into those 65 patients whose endometrial tissues were further subjected to immunohistochemical analysis) as described previously (19). Briefly, questionnaires on dysmenorrhea and other clinical information were administered before surgery during the hospital stay.…”

Section: Methodsmentioning

confidence: 99%

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Zhou

et al. 2012

Molecular & Cellular Proteomics

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Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia, and infertility in 8.8 -61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a two-dimensional polyacrylamide gel electrophoresis/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial to mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial to mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a ␤-catenin/T-cell factor (Tcf) signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1␣/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis, and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients.

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Section: Methodsmentioning

confidence: 99%

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Zhou

et al. 2012

Molecular & Cellular Proteomics

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“…The patients recruited to this study were reported previously [19,21]. Briefly, 50 women with histologically confirmed adenomyosis (excluding endometriosis) seen at Shanghai Obstetrics and Gynecology Hospital, Fudan University, were recruited for this study.…”

Section: Methodsmentioning

confidence: 99%

“…All endometrial samples were grouped either in proliferative or secretory phase based on Noyes’ dating criteria, as previously reported [21]. In women with adenomyosis and without, exactly half of them were in the secretory phase.…”

Section: Methodsmentioning

confidence: 99%

“…In women with adenomyosis and without, exactly half of them were in the secretory phase. Their amount of menses during menstruation was grouped into three classes: light, moderate, and heavy, and the severity of dysmenorrhea was classified as mild, moderate, and severe, as reported previously [19,21]. …”

Section: Methodsmentioning

confidence: 99%

“…We also correlated their immunoreactivity levels with the patients’ symptomology such as dysmenorrhea status and/or severity, amount of menses, and uterus size. Finally, we evaluated correlation coefficients of the DNMT immunoreactivity levels with other proteins that we have reported previously, including NF-ĸB [19], SLIT [20], oxytocin receptor (OTR) and transient receptor potential vanilloid type 1 (TRPV1) [21]. This may provide some much needed clues suggesting that some of these aberrations may be epigenetically controlled.…”

Section: Introductionmentioning

confidence: 99%

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Aberrant Immunoreactivity of Deoxyribonucleic Acid Methyltransferases in Adenomyosis

Liu

Guo²

2012

Gynecol Obstet Invest

Self Cite

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Objectives: To investigate the expression and localization of deoxyribonucleic acid methyltransferases (DNMTs) in women with and without adenomyosis. Study Design: Ectopic and homologous eutopic endometrium from 50 women with adenomyosis and endometrium from 18 age- and menstrual phase-matched women without adenomyosis were used for immunohistochemical analysis. Tissue sections were immunostained with DNMT1, DNMT3A, and DNMT3B. Microscopic evaluation to assess the presence and localization of DNMT1, DNMT3A, and DNMT3B throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis was performed, and comparison with normal endometrium was made. Results: Compared with normal endometrium, immunoreactivity to DNMT1 and DNMT3B was higher in ectopic endometrium, while DNMT3A staining levels were significantly reduced in both eutopic and ectopic endometrium. DNMT1 immunoreactivity in eutopic endometrium was positively associated with heavier menses. Increased DNMT3B immunoreactivity in ectopic, but not eutopic, endometrium was associated with the severity of dysmenorrhea. Conclusions: The immunoreactivity to DNMTs in adenomyosis differs significantly from that in normal endometrium, suggesting that adenomyosis may be an epigenetic disease. The finding that DNMT3B correlates with the severity of dysmenorrhea suggests that DNMTs may be involved in adenomyosis-caused dysmenorrhea and its severity. Thus, therapeutics based on epigenetic rectification may hold promise in the management of adenomyosis.

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Insights on Adenomyosis Development

Vannuccini

Clemenza

2022

Endometriosis and Adenomyosis

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Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis

Cited by 68 publications

References 33 publications

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Aberrant Immunoreactivity of Deoxyribonucleic Acid Methyltransferases in Adenomyosis

Insights on Adenomyosis Development

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