Prevalence and Impact of Chronic Endometritis in Patients With Intrauterine Adhesions: A Prospective Cohort Study

Chen, Yuqing; Liu, Lixiang; Luo, Yang; Chen, Ming‐Hui; Yang, Huan; Fang, Ruili

doi:10.1016/j.jmig.2016.09.022

Cited by 53 publications

(46 citation statements)

References 23 publications

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“…Обращает на себя внимание тот факт, что наиболее тяжелая степень обнаружена у пациенток с диагностическим выскабливанием без гистероскопического контроля, что подтверждает ятрогенный характер инициации процесса. Роль инфекции в патогенезе внутриматочных синехий неубедительна, однако исходя из наших данных о высокой частоте перенесенного хронического эндометрита в анамнезе, а также разультатов эхографического и гистологического исследований во всех исследуемых группах, можно рассматривать инфекционный фактор как один из основных факторов риска развития внутриматочных синехий, что подтверждают данные авторов [17][18][19].…”

Section: Discussionunclassified

Clinical, anamnestic data and treatment results in women with intrauterine adhesions

Khirieva¹,

Adamyan²

2017

Probl. reprod.

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Section: Discussionunclassified

Clinical, anamnestic data and treatment results in women with intrauterine adhesions

Khirieva¹,

Adamyan²

2017

Probl. reprod.

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“…Although combined hysteroscopic synechialysis with a series of postoperative adjuvant strategies can normalize the morphology of the uterine cavity to various extents, and can even increase or restore the menstrual ow of some patients, the available therapeutic interventions for IUA are either insu ciently effective or unsound in the clinical setting, with the main problems including postoperative adhesion recurrence and infertility [4][5][6]. Postoperatively, the recurrence rate of IUAs is as high as 62.5% [7], whereas the overall pregnancy rate is only 42.8-66.1% [8]. According to China's national conditions and humanistic ethics, stem cell use in reproduction and surrogacy is not legally allowed; therefore, focusing on the biological mechanism and aiming to seek targeted treatments for endometrial brosis during the formation of IUA should be considered priorities.…”

Section: Introductionmentioning

confidence: 99%

si-SNHG5-FOXF2 inhibits TGF-β1-induced fibrosis in human primary endometrial stromal cells by the Wnt/β-catenin signalling pathway

Liu

Chen

et al. 2020

Preprint

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Background: Intrauterine adhesions (IUAs) are manifestations of endometrial fibrosis characterized by inflammation and fibrinogen aggregation in the extracellular matrix (ECM). The available therapeutic interventions for IUA are insufficiently effective in the clinical setting for postoperative adhesion recurrence and infertility problems. In this study, we investigated whether si-SNHG5-FOXF2 can serve as a molecular mechanism for the inhibition of IUA fibrosis ex vivo.Methods: FOXF2, TGF-β1 and collagen expression levels were measured by microarray sequencing analysis in three normal endometrium groups and six IUA patients. We induced primary human endometrial stromal cells (HESCs) into myofibroblasts (MFs) to develop an IUA cell model with various concentrations of TGF-β1 at various times. Downstream target genes of FOXF2 were screened by chromatin immunoprecipitation combined with whole-genome high-throughput sequencing (ChIP-seq). We investigated ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs with FOXF2 downregulation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB), immunohistochemistry (IHC), flow cytometry, ethylenediurea (EdU) and CCK8 assays. We identified lncRNA SNHG5 as the upstream regulatory gene of FOXF2 through RNA immunoprecipitation (RIP), RNA pulldown and fluorescence in situ hybridization (FISH). Finally, we examined FOXF2 expression, ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs upon FOXF2 downregulation.Results: FOXF2 was highly expressed in the endometrium of patients with IUA. Treatment of primary HESCs with 10 ng/ml TGF-β1 for 72 h was found to be most effective for developing an IUA cell model. FOXF2 regulated multiple downstream target genes, including collagen, vimentin (VIM) and cyclin D2/DK4, by ChIP-seq and ChIP-PCR. FOXF2 downregulation inhibited TGF-β1-mediated primary HESC fibrosis, including ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related protein expression. We identified lncRNA SNHG5 as an upstream gene that directly regulates FOXF2 by RIP-seq, qRT-PCR, WB, and FISH. SNHG5 downregulation suppressed FOXF2 expression in the IUA cell model, resulting in synergistic repression of the Wnt/β-catenin pathway, thereby altering TGF-β1-mediated ECM aggregation in endometrial stromal cells ex vivo. Conclusions: Regulation of the Wnt/β-catenin signalling pathway and ECM formation by si-SNHG5-FOXF2 effectively inhibited the profibrotic effect of TGF-β1 on primary HESCs. This finding can provide a molecular basis for antagonizing TGF-β1-mediated fibrosis in primary HESCs.

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“…Although combined hysteroscopic synechialysis with a series of postoperative adjuvant strategies can normalize the morphology of the uterine cavity to various extents and can even increase or restore the menstrual ow of some patients, the available therapeutic interventions for IUA are either insu ciently effective or unsound in the clinical setting, with the main problems including postoperative adhesion recurrence and infertility [4][5][6]. Postoperatively, the recurrence rate of IUAs is as high as 62.5% [7], whereas the overall pregnancy rate is only 42.8-66.1% [8]. According to China's national conditions and humanistic ethics, stem cell use in reproduction and surrogacy is not legally allowed; therefore, focusing on the biological mechanism and aiming to seek targeted treatment for endometrial brosis during the formation of IUA should be considered priorities.…”

Section: Introductionmentioning

confidence: 99%

si-SNHG5-FOXF2 Inhibits TGF-β1-induced Fibrosis in Human Primary Endometrial Stromal Cells by Wnt/β-catenin Signaling Pathway

Liu

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Intrauterine adhesions (IUAs) are manifestations of endometrial fibrosis characterized by inflammation and fibrinogen aggregation in the extracellular matrix (ECM). The available therapeutic interventions for IUA are insufficiently effective in the clinical setting for postoperative adhesion recurrence and infertility problems. In this study, we investigated si-SNHG5-FOXF2 can serve as a molecular mechanism for inhibition of IUA fibrosis ex vivo.Methods: FOXF2, TGF-β1 and collagens expression levels were measure by a Microarray sequencing analysis in three normal endometrium group and six IUA patients. We induced primary HESCs into MFs to develop an IUA cell model with various concentrations of TGF-β1 at various times. Downstream target genes for FOXF2 were screened by chromatin immunoprecipitation combined with whole- genome high-throughput sequencing (ChIP-seq). We investigated ECM formation, cell proliferation and Wnt/β-catenin signaling pathway-related proteins in primary HESCs with FOXF2 downregulation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB), immunohistochemistry (IHC), Flow cytometry, EdU and CCK8 assays. We identified lncRNA SNHG5 as the upstream regulatory gene of FOXF2 through RNA immunoprecipitation (RIP), RNA-pulldown and FISH. Finally, we examined FOXF2 expression, ECM formation, cell proliferation and Wnt/ β-catenin signaling pathway-related proteins in primary HESCs with FOXF2 downregulation.Results: FOXF2 was highly expressed in endometrium from patients with IUA. Treatment of primary HESCs with 10ng / ml TGF-β1 for 72 h was found to be most effective for developing an IUA cell model. FOXF2 regulated multiple downstream target genes including collagen, VIM and cyclin D2/DK4 by ChIP-seq and ChIP-PCR. FOXF2 downregulation inhibited TGF-β1-mediated primary HESC fibrosis including ECM formation, cell proliferation and Wnt/β-catenin signaling pathway-related proteins expressions. We identified lncRNA SNHG5 as an upstream gene that directly regulated FOXF2 by RIP-seq, qRT-PCR, WB and FISH. SNHG5 downregulation suppressed FOXF2 expression in the IUA cell model, resulting in synergistic repression of Wnt/β-catenin signaling pathway activation and thereby altering TGF-β1-mediated ECM aggregation in endometrial stromal cells ex vivo. Conclusions: Regulation of the Wnt/β-catenin signaling pathway and ECM formation by si-SNHG5-FOXF2 effectively inhibited the profibrotic effect of TGF-β1 on primary HESCs. It can provide a molecular basis for antagonizing TGF-β1-mediated fibrosis in primary HESCs.

show abstract

Prevalence and Impact of Chronic Endometritis in Patients With Intrauterine Adhesions: A Prospective Cohort Study

Cited by 53 publications

References 23 publications

Clinical, anamnestic data and treatment results in women with intrauterine adhesions

Clinical, anamnestic data and treatment results in women with intrauterine adhesions

si-SNHG5-FOXF2 inhibits TGF-β1-induced fibrosis in human primary endometrial stromal cells by the Wnt/β-catenin signalling pathway

si-SNHG5-FOXF2 Inhibits TGF-β1-induced Fibrosis in Human Primary Endometrial Stromal Cells by Wnt/β-catenin Signaling Pathway

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