Investigation of spontaneous pelvic organ prolapse in the rhesus macaque model
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PROVIDER: PRJNA852604 | ENA |
REPOSITORIES: ENA
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Project description:An appropriate model is urgently required for pathological mechanism investigation of pelvic organ prolapse and the development of new therapeutic strategies. It is generally thought that damage to the vagina and its supportive tissues due to vaginal birth, menopause, and so on can result in loss of vaginal support and prolapse of the pelvic organs. Currently, ovariectomy and simulated vaginal delivery in animal models are applied to mimic the status of menopause and induce vaginal injury, however, the complex biochemical and biomechanical changes induced by vaginal delivery and prolapse is difficultly achieved by these methods. The rhesus macaque shares many features similarly to women, such as pelvic floor anatomy and parturition, and makes an excellent experimental model for the study of prolapse. Besides, the rhesus macaque develops prolapse spontaneously. Thus, there has great value to investigate the changes of spontaneous prolapse and make them animal models for the study of prolapse. In this study, we will assess the histomorphology, biochemical property and biomechanical property of prolapsed vagina. And then, cell atlas of normal and prolapsed vagina will be constructed by single-cell transcriptome sequencing. We will reveal the cell type specific molecular mechanisms. This study will improve the understanding of spontaneous prolapse in the rhesus macaque and provide fundamental data for the application of spontaneous prolapse as animal models to study POP.
2024-12-31 | GSE206919 | GEO
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates M-bM-^IM-$5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison This was a group matched case control study of 8 women with pelvic organ prolapse versus 9 non-prolapse controls, both undergoing hysterectomy for benign conditions. Two separate pelvic support tissues were collected from each patient. The uterosacral ligament and round ligament tissue was removed at the time of hysterectomy, RNA was extracted and ABI whole genome chips used to identify differences in expression profiles of individual samples. Various ethnic groups, age groups and menopausal status were included.
2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress
Project description:Profiles of Pelvic organ prolapse
| PRJNA859003 | ENA
Project description:Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study was to identify differentially expressed proteins in the uterosacral ligaments of women with and without pelvic organ prolapse and analyze their relationships to cellular mechanisms involved in the pathogenesis of pelvic organ prolapse. Experimental Design: Uterosacral ligament connective tissue from four patients with pelvic organ prolapse and four control women underwent iTRAQ analysis followed by Ingenuity Pathway Analysis of differentially expressed proteins. Differentially expressed proteins were valideated using western blot analysis. Results: A total of 1789 unique protein sequences were identified in the uterosacral ligament connective tissues. 88 proteins had expression levels that were significantly different between prolapse and control groups (≥1.2-fold). Ingenuity pathway analysis demonstrated 14 differentially expressed proteins that were associated with "Connective Tissue Function". Among them, fibromodulin(FMOD), Collagen alpha-1 (XIV) chain(COL14A1), Calponin-1 (CNN-1), Tenascin (TNC), and Galectin-1(LGALS1 appeared most likely to play a role in the etiology of pelvic organ prolapse. Conclusions and clinical relevence: We identified at least 6 proteins not previously associated with the pathogenesis of pelvic organ prolapse with biologic functions that suggest a plausible relationship to the disorder. These results may be helpful for furthering our understanding of the pathophysiological mechanisms of pelvic organ prolapse.
2018-12-10 | PXD011467 | Pride
Project description:Pelvic organ prolapse (POP) affects a large proportion of adult women. With the increase in global population ageing, the prevalence of POP is expected to increase in upcoming decades, which will impose a substantial medical burden. Therefore, suitable therapeutical target is important. However, due to the pathogenesis of POP is still unclear, it leads to the failure of POP repair. Herein, we identified changes in ncRNA, and mRNAs in the anterior vaginal wall and uterosacral ligament in patients with POP, providing new insights into the pathogenesis of POP and new targets for treatment.
2022-09-05 | GSE208264 | GEO
Project description:Profiles of Pelvic organ prolapse [miRNA-seq]
| PRJNA858990 | ENA
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates ≤5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison
2008-09-20 | GSE12852 | GEO
Project description:Pelvic organ prolapse (POP) affects a large proportion of adult women. With the increase in global population ageing, the prevalence of POP is expected to increase in upcoming decades, which will impose a substantial medical burden. Therefore, suitable therapeutical target is important. However, due to the pathogenesis of POP is still unclear, it leads to the failure of POP repair. Herein, we identified changes in ncRNA, and mRNAs in the anterior vaginal wall and uterosacral ligament in patients with POP, providing new insights into the pathogenesis of POP and new targets for treatment.
2022-09-05 | GSE208261 | GEO
Project description:Pelvic organ prolapse (POP) is a common multifactorial disease in a heterogeneous population of women. Due to this heterogeneity, the underlying molecular mechanisms contributing to the pathogenesis of POP are still unclear. We sought to identify dysregulated pathways by comparing gene expression profiles of prolapsed and non- prolapsed anterior vaginal wall tissue within the same patient. Biopsies were collected from 12 premenopausal women undergoing prolapse surgery (cystocele POP-Q stage ≥ 2). A full thickness anterior vaginal wall sample was taken from the POP site during anterior colporrhaphy. An additional sample was taken from the non-prolapsed apex of the anterior vaginal cuff. Micro-array analysis was performed using whole genome GE 4x44K microarrays. Beside a significance analysis of micro-array (SAM), also a visual cluster analysis was performed. 12 women with POP: 12 biopsies anterior vaginal wall (POP site) versus 12 biopies precervical anterior vaginal wall ( non POP site)
2015-07-31 | E-GEOD-53868 | biostudies-arrayexpress
Project description:Failure of ligamentous support of the genital tract to resist intra-abdominal pressure is a plausible underlying mechanism for the development of pelvic organ prolapse, but the nature of molecular response of pelvic tissue support remains unknown. We hypothesized that the expression of genes coding for proteins involved in maintaining the cellular and extracellular integrity would be altered in cases of pelvic organ prolapse. Therefore, cDNA microarrays were used to examine the difference in transcriptional profile in RNA of primary culture fibroblasts subjected to mechanical stretch and those that remained static. Keywords: Changes in transcription profile in pelvic organ fibroblasts in response to stretch
2007-01-26 | GSE6862 | GEO