Pathogenesis Of Pelvic Organ Prolapse Research Articles

SIRT1 as a potential therapeutic target in pelvic organ prolapse due to protective effects against oxidative stress and cellular senescence in human uterosacral ligament fibroblasts.

The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro. Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences. Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720. SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.

4D DIA-PRM proteomic study identifying modulated pathways and biomarkers associated with pelvic organ prolapse

Pelvic organ prolapse (POP) is a highly disabling condition that negatively affects the quality of life of millions of women worldwide. However, the underlying mechanisms associated with the development and progression of the disease remain poorly understood. Here, an untargeted four-dimensional data-independent acquisition (4D DIA)-based proteomics approach was applied to vaginal wall tissue samples from POP (n = 19) and control (n = 8) patients to identify potential diagnostic biomarker(s) for POP and examine the molecular mechanisms underlying the disease. Of the 5713 tissue proteins that were detected, 1957 proteins were significantly changed in POP patients. Further bioinformatics analysis revealed that multiple biological processes including protein digestion & absorption, retrograde endocannabinoid signaling, tyrosine metabolism, and nucleotide metabolism were significantly enriched and associated with the pathogenesis of POP. Interestingly, 16 of these differentially expressed proteins associated with four pathways were also identified by targeted parallel reaction monitoring (PRM) proteomics analysis on the same 27 tissue samples. Changes in 94 % (15/16) of these proteins were consistent with the 4D DIA data. Furthermore, most proteins displayed good diagnostic accuracy with high area under the curve (AUC) values (AUC＞0.8). Specifically, five proteins including ELN, COL6A2, ENTPD1, AOC3, and COX7A2 distinguished between POP and control patients with very high accuracy (AUC ≥ 0.95) in both 4D DIA and PRM analyses, and may therefore be potential diagnostic biomarkers for POP. In summary, the present study not only provided several potential biomarker(s) for effective POP diagnosis, but extended our knowledge of the key regulatory pathways associated with the disease.

Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women's quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-β/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.

Bioinformatic analysis of biological changes involved in pelvic organ prolapse.

The molecular mechanisms involved in the pathogenesis of pelvic organ prolapse (POP) remain unclear. This study aimed to identify key molecules involved in the pathogenesis and progression of POP. Differentially expressed genes (DEGs) were identified based on gene expression data extracted from the GSE53868, GSE28660, and GSE12852 datasets in the gene expression omnibus database. The R software was used for data mining, and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to explore the biological functions of DEGs. A protein-protein interaction network (PPI) was constructed using the Search Tool for the Retrieval of Interacting Genes database, and hub genes were identified by the Cytoscape plug-in cytoHubba. In addition, the CIBERSORT algorithm was used to analyze and evaluate immune cell infiltration in POP tissues. A total of 92 upregulated DEGs were identified and subjected to enrichment analysis. Gene ontology analysis revealed that these DEGs were associated with response to hormones, positive regulation of cell death, collagen-containing extracellular matrix, and extracellular matrix. Kyoto encyclopedia of genes and genomes pathway analysis showed that the upregulated genes were mainly enriched in the phosphatidylinositol 3-kinase-AKT signaling pathway. The PPI network was structured. Nodes in the PPI network were associated with structural molecular activity and collagen-containing extracellular matrix. A total of 10 hub genes were identified, namely, CDKN1A, IL-6, PPARG, ADAMTS4, ADIPOQ, AREG, activating transcription factor 3, CCL2, CD36, and Cell death-inducing DNA fragmentation factor-like effector A. Furthermore, patients with POP were found to have a higher abundance of CD8-positive T cells in the 3 gene expression omnibus datasets. The abundance of CD8-positive T cells was negatively correlated with that of follicular helper T cells (Pearson correlation coefficient = -0.34, P < .01) or gamma delta T cells (Pearson correlation coefficient = -0.33, P < .01). But was positively correlated with that of M2 macrophages (Pearson correlation coefficient = 0.35, P < .01) and activated memory CD4 T cells (Pearson correlation coefficient = 0.34, P < .01). Altogether, PPARG, ADAMTS4, ADIPOQ, AREG, CD36, and Cell death-inducing DNA fragmentation factor-like effector A genes were discovered in the POP process for the first time, which should be intensively investigated.

Current practice in animal models for pelvic floor dysfunction.

The objective was to explore the current practice of using animal models for female pelvic floor dysfunction (PFD). By applying PFD and animal models as the keywords, we made a computerized search using PubMed, Ovid-Medline and Ovid-Embase from 2000 to 2022. The publications on the construction and application of animal models for PFD were included, and the results are presented in narrative text. Studies on PFD primarily use rodents, large quadrupeds, and nonhuman primates (NHPs). NHPs are closest to humans in anatomy and biomechanics of the pelvic floor, followed by large quadrupeds and rodents. Rodents are more suitable for studying molecular mechanism, histopathology of PFD, and mesh immune rejection. Large quadrupeds are adaptable to the study of pelvic floor biomechanics and the development of new surgical instruments for PFD. NHPs are suitable for studying the occurrence and pathogenesis of pelvic organ prolapse. Among modeling methods, violent destruction of pelvic floor muscles, regulation of hormone levels, and denervation were used to simulate the occurrence of PFD. Gene knockout can be used to study both the pathogenesis of PFD and the efficacy of treatments. Other methods such as abdominal wall defect, vaginal defect, and in vitro organ bath system are more frequently used to observe wound healing after surgery and to verify the efficacy of treatments. The rat is currently the most applicable animal type for numerous modeling methods. Vaginal dilation is the most widely used modeling method for research on the pathogenesis, pathological changes, and treatment of PFD.

Transcriptome and metabolome analyses reveal the interweaving of immune response and metabolic regulation in pelvic organ prolapse.

The pathogenesis of pelvic organ prolapse (POP) remains unknown. Herein, we aim to reveal the molecular profile of POP by transcriptomic and metabolomic analysis. We selected 12 samples of uterosacral ligaments (USLs) from 6 POP patients and 6 controls for transcriptomic and metabolomic analyses. Differentially expressed genes (DEGs) were identified using the R package edgeR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using clusterProfiler, and a protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. Metabolomic profiling was performed by a liquid chromatography-tandem mass spectrometry system. Transcriptomic analysis identified 487 DEGs between the POP and control groups. Functional enrichment analysis revealed that they were mostly related to immune response terms, including "adaptive immune response," "T cell differentiation," and "T cell activation." In addition, PTPRC, LCK, CD247, IL2RB, CD2, CXR5, JUN, CD3E, IL2RG, and PRF1 were the 10 nodes with the highest node degrees in the PPI network. Metabolomic profiling revealed 290 differentially expressed metabolites, which significantly enriched in "glycerophospholipid metabolism," "nicotinate and nicotinamide metabolism," "glycine, serine, and threonine metabolism," "arginine and proline metabolism," "pyrimidine metabolism," and "purine metabolism." Finally, integrated analysis revealed that the DEGs involved in these significantly enriched metabolic pathways included NT5C1A, GMPR, SDS, ALAS2, CARNS1, PYCR1, P4HA3, PGS1, and NMRK2. Our findings demonstrate that the immune response and metabolic regulatory pathways are intertwined in POP and might provide new therapeutic targets.

Advanced glycation end products (AGEs) downregulate the miR-4429/PTEN axis to promote apoptosis of fibroblasts in pelvic organ prolapse.

BackgroundPelvic organ prolapse (POP) is a common degenerative disease among females. We previously reported that advanced glycation end products (AGEs), compounds derived from nonenzymatic glycoxidation reactions, accumulated in the human vaginal wall and impaired the function of fibroblasts in the pathogenesis of POP. This study investigated the apoptosis induced by AGEs in human uterosacral ligament fibroblasts and the underlying mechanism.MethodsHuman uterosacral ligament fibroblasts were cultured and identified. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to identify the expression of miR-4429, phosphatase and tensin homolog (PTEN), and caspase-3. Flow cytometric analysis was applied to detect the apoptosis rate of fibroblasts. Dual-luciferase reporter assay was performed to verify the relationship between miR-4429 and PTEN. The overexpression of miR-4429 and the inhibition of PTEN were achieved by cell transfections. Western blot analysis was used to detect the protein levels of PTEN, phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt).ResultsThe AGEs promoted fibroblast apoptosis both in the POP and the non-POP groups. The expression of PTEN increased in fibroblasts from the POP group or fibroblasts treated with AGEs. It was confirmed that miR-4429 interacted with PTEN messenger RNA (mRNA), and the expression level of miR-4429 was reduced in fibroblasts from the POP group or fibroblasts treated with AGEs. Further, overexpression of miR-4429 alleviated increased PTEN expression and fibroblast apoptosis induced by AGEs. Similarly, inhibition of PTEN expression alleviated increased fibroblast apoptosis induced by AGEs. In addition, the protein expressions of PI3K and phosphorylated Akt were reduced in fibroblasts exposed to AGEs.ConclusionsWe proposed that AGEs induced fibroblast apoptosis by regulating the miR-4429/PTEN/PI3K/Akt pathway in POP. Our results revealed a novel mechanism by which AGEs contributed to the molecular pathological alteration in POP.

Expression of CD44, Transforming Growth Factor-β, and Matrix Metalloproteinases in Women WithPelvic Organ Prolapse.

BackgroundDefects in the pelvic floor connective tissue may underlie the etiology of pelvic organ prolapse (POP). We hypothesized that the expression of proteins regulating extracellular matrix turnover is altered in the uterosacral ligament of women with POP. We compared the expression of CD44, transforming growth factor (TGF)-β, and matrix metalloproteinases (MMPs) 2/9 in women with and without POP.Methods and ResultsThis matched case-control study included 30 postmenopausal women, with POP stage 2 and higher according to the POP quantification system, and 30 postmenopausal women without POP. Immunohistochemical analyses of the uterosacral ligament specimens obtained after hysterectomy were performed to determine CD44, TGF-β, MMP-2, and MMP-9 expression. The expression was quantified using ImageJ software, and the association between prolapse occurrence and risk factors was evaluated using Spearman's correlation analysis. CD44 expressions were significantly lower (p < 0.05), whereas MMP-2 and MMP-9 expression was higher (p < 0.0001 and p < 0.05, respectively), in the POP group than in the control group. The expression of TGF-β was similar in both groups. The occurrence of uterine prolapse was positively correlated with age, postmenopausal age, and MMP-2 and MMP-9 expression (p < 0.01) and negatively correlated with CD44 expression (p < 0.05).ConclusionCD44, MMP-2, and MMP-9 may play critical roles in the pathogenesis of POP and may be candidate biomarkers of POP progression.

Structural, functional and molecular pathogenesis of pelvic organ prolapse in patient and Loxl1 deficient mice

Pelvic organ prolapse is a worldwide health problem to elderly women. Understanding its pathogenesis and an ideal animal model are crucial to developing promising treatments. The present study aimed to investigate new clinical significance and detailed mechanism of pelvic organ prolapse by comparing the structural, functional and molecular dysfunctions of pelvic organ prolapse in patient and Loxl1 deficient mice. Our results showed that human vagina tissues from prolapsed site showed disarranged collagen and elastic fibers compared with the non-prolapse tissue. A gene ontology (GO) analysis of differentially expressed genes revealed molecular changes mainly related to inflammatory response and extracellular matrix (ECM) organization. While the mice lacking Loxl1 developed stable POP phenotype and disordered ECM structure in histology. Such Loxl1 knockout mice exhibited a significantly urinary dysfunction and decreased mechanical properties of the pelvic floor tissues, implying that POP in human condition might be induced by progressively decreased mechanics of pelvic tissues following ECM catabolism. Similarly, we not only identified significant up-regulated ECM catabolism processes and down-regulated ECM synthesis processes, but also characterized high level of inflammatory response in vagina tissue of the Loxl1 deficient mice. Thus, all these pathological changes in the POP mice model was consistent with those of the clinical elderly patients. These findings provide new insight into remodeling of POP by LOXL1 regulation and be of great importance to develop combination treatments of ECM metabolism and inflammation regulation strategy.

Pathogenesis of vaginal prolapse with the formation of rectocele: a review

To carry out a systematic analysis of the data available in the modern literature on the pathogenesis of the formation of vaginal prolapse with the formation of rectocele rectum. The failure of the pelvic floor, namely its posterior compartment with the formation of a rectocele against the background of the lowering of the posterior vaginal wall, continues to be one of the most common gynecological diseases. This article presents an analysis of current literature data on the pathogenesis of pelvic organ prolapse with the formation of rectocele. Analyzing the above-mentioned data, it can be noted that the research data of recent years have significantly expanded the understanding of the etiology and pathogenesis of pelvic organ prolapse in its posterior compartment. However, the issues of etiology and pathogenesis of genital prolapse in patients of reproductive age, the role of individual risk factors and their combinations, pathogenetic mechanisms of development are still far from being resolved. Unfortunately, none of the above theories fully explains all the reasons for the formation of pelvic organ prolapse in its posterior compartment.

ATF3 regulates oxidative stress and extracellular matrix degradation via p38/Nrf2 signaling pathway in pelvic organ prolapse

Pelvic organ prolapse (POP) is a common disorder in women, and it is characterized by weakening of pelvic supportive structure with extracellular matrix (ECM) degradation. Activating transcription factor 3 (ATF3) was upregulated in anterior vaginal wall tissues of POP patients. We hypothesized that upregulation of ATF3 might contribute to POP development. This study aims to unveil the role of ATF3 in the pathogenesis of POP using a H2O2-induced in vitro model. Vaginal fibroblasts were isolated from woman with POP-Q stage greater than II and asymptomatic women with normal pelvic floor support. Knockdown of ATF3 enhanced cell viability and decreased cell apoptosis. Flow cytometry and immunnofluorescence showed that ATF3 deficiency inhibited H2O2-induced ROS production and the expression of 8 OHdG and 4-HNE. Western blot and Real-time PCR analysis revealed that ATF3 deficiency attenuated ECM component degradation (increasing collagen I, collagen III and elastin) and MMPs/TIMPs imbalance (decreasing MMP2 and MMP9 and increasing TIMP2). Moreover, knockdown of ATF3 induced the activation of p38/Nrf2/HO-1 signaling pathway. Further treatment with p38 inhibitor SB203580 abolished the protection of ATF3 deficiency against H2O2-induced cell damage, which was reverted by Nrf2 activator TBHQ. Thus, ATF3 likely contributes to POP progression by inducing cell apoptosis, oxidative stress and ECM degradation via regulating p38/Nrf2 pathway, which provides a potential therapeutic target for POP.

Effects of the decrease of β-catenin expression on human vaginal fibroblasts of women with pelvic organ prolapse.

Pelvic organ prolapse (POP) lowers the quality of life in elderly women, and there have been no studies on its role in the pathogenesis of POP. The purpose of this study is to investigate the effect of β-catenin on proliferation and collagen anabolism in human vaginal fibroblasts (HVFs). The adherence and differential adherence methods were used to culture and purify HVFs. RNA interference was applied to knockdown β-catenin and lithium chloride was used to activate Wnt/β-catenin signaling pathway. β-catenin nuclear translocation was tested by immunofluorescence, and HVF proliferation was detected by performing MTT assays. The expression of β-catenin, phosphorylated-β-catenin, phosphorylated-glycogen synthase kinase 3β (p-GSK3β), collagen I, matrix metalloproteinase 2 (MMP2), and tissue-derived inhibitors of metalloproteinases 2 (TIMP2) was assessed by western blot analysis. The expression of β-catenin and collagen I was lower in HVFs of POP group than that of control group. The proliferation rate of HVFs in POP group was lower than that in control group. Knockdown of β-catenin decreased the cell proliferation rate and the expression of collagen I. Lithium chloride can activate the Wnt/β-catenin signaling pathway. β-catenin participates in the proliferation and collagen I synthesis of HVFs. The decrease of β-catenin expression may be closely related to the occurrence, and development of POP. LiCl can activate the Wnt/β-catenin signaling pathway in HVFs and thus increase HVFs proliferation and collagen synthesis.

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse

Introduction and hypothesisFamily and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations.MethodsUpdating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria.ResultsWe screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at the ESR1 gene (OR 0.67 95% CI 0.46–0.98, I2 = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11–1.82, I2 = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39–0.96, I2 = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66–0.96, I2 = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies.ConclusionThe genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.

Expression of COX-2 and Nrf2/GPx3 in the anterior vaginal wall tissues of women with pelvic organ prolapse.

To evaluate COX-2 and Nrf2/GPx3 expressions in the lamina propria of the anterior vaginal wall tissues of women with and without pelvic organ prolapse (POP). Tissue samples of anterior vaginal wall were examined using HE staining, immuohistochemical staining and Western blot for the expressions of COX-2/PGE2, Nrf2/GPx3, MMP2, TIMP1, collagen I and collagen III (n = 35, per group). Compared with control group, collagen fibers of the anterior vaginal wall were disorganized and discontinuous. Expressions of Nrf2, GPx3, TIMP1, collagen I and collagen III were found significantly lower in POP group (P < 0.05); while, expressions of COX-2, PGE2, and MMP2 were found significantly higher in POP group (P < 0.05). Statistically significant correlations of COX-2 and Nrf2/GPx3 were showed (P < 0.01). We found that the interaction between inflammation and oxidative stress was closely related to the development of POP. This study demonstrates that COX-2 and Nrf2 pathways may be involved in pathogenesis of POP, as promising potential therapeutic targets and agents.

Oxidative Stress: A Possible Trigger for Pelvic Organ Prolapse.

Pelvic organ prolapse is a frequent health problem in women, encountered worldwide, its physiopathology being still incompletely understood. The integrity of the pelvic-supportive structures is a key element that prevents the prolapse of the pelvic organs. Numerous researchers have underlined the role of connective tissue molecular changes in the pathogenesis of pelvic organ prolapse and have raised the attention upon oxidative stress as an important element involved in its appearance. The advancements made over the years in terms of molecular biology have allowed researchers to investigate how the constituent elements of the pelvic-supportive structures react in conditions of oxidative stress. The purpose of this paper is to underline the importance of oxidative stress in the pathogenesis of pelvic organ prolapse, as well as to highlight the main oxidative stress molecular changes that appear at the level of the pelvic-supportive structures. Sustained mechanical stress is proven to be a key factor in the appearance of pelvic organ prolapse, correlating with increased levels of free radicals production and mitochondrial-induced fibroblasts apoptosis, the rate of cellular apoptosis depending on the intensity of the mechanical stress, and the period of time the mechanical stress is applied. Oxidative stress hinders normal cellular signaling pathways, as well as different important cellular components like proteins, lipids, and cellular DNA, therefore significantly interfering with the process of collagen and elastin synthesis.

The role of enhancing lipid peroxidation in the pathogenesis of pelvic organ prolapse in women

The role of enhancing lipid peroxidation in the pathogenesis of pelvic organ prolapse in women

Evaluating Pelvic Floor Muscle Contractility Using Two-Dimensional Transperineal Ultrasonography in Patients With Pelvic Organ Prolapse

(Abstracted from Neurourol Urodyn 2019;38:1363–1369) Pelvic function has a significant role in the pathogenesis of pelvic organ prolapse (POP). First-line treatment for POP is pelvic floor muscle training (PFMT), which is widely prescribed for this purpose.

Effect of Protease Inhibitors in Healing of the Vaginal Wall

Impaired elastogenesis and increased degradation of elastic fibers has been implicated in the pathogenesis of pelvic organ prolapse. Loss of the elastogenic organizer, fibulin-5 (FBLN5), leads to pelvic organ prolapse in mice. The objective of this study was to investigate the regulation of FBLN5 after surgical injury of the vaginal wall using the rat as a preclinical animal model. Both endogenous and recombinant FBLN5 were degraded after surgical injury. Estrogen did not alter the dramatic loss of vaginal FBLN5 in the acute phase after injury (12–48 h), but resulted in rescue of the poor recovery of FBLN5 levels in the late phase (7 d) of healing in ovariectomized animals. In contrast with estrogen, the general MMP inhibitor, actinonin, abrogated injury-induced degradation of FBLN5 significantly. Further, actinonin rescued the negative effects of injury on biomechanics, histomorphology, and elastic fibers. Control of excessive matrix degradation by local application of actinonin at the time of surgery may lead to improved elastic fiber regeneration and wound healing, thereby potentially enhancing pelvic floor recovery after reconstructive surgery for prolapse.

Pelvic floor ultrasound: Essentials

Female pelvic floor dysfunction encompasses a number of prevalent conditions and includes pelvic organ prolapse, urinary and fecal incontinence, obstructed defecation and sexual dysfunction. In most cases neither etiology nor pathophysiology are well understood. Imaging has great potential to enhance both research and clinical management capabilities, and to date this potential is under-utilised. Of the available techniques such as X-ray, computed tomography, magnetic resonance imaging and ultrasound, the latter is generally superior for pelvic floor imaging, especially in the form of perineal or translabial imaging. The technique is safe, simple, cheap, easily accessible and provides high spatial and temporal resolutions. The commonest indication for pelvic floor imaging is female pelvic organ prolapse. Translabial realtime ultrasound during a Valsalva maneuver will demonstrate cystocele, uterine prolapse, rectocele, enterocele and rectal intussusception and allow quantification against the inferoposterior symphyseal margin. The introduction of 3D/4D imaging has allowed us to diagnose major pelvic floor trauma (‘avulsion’) and overdistension of the levator hiatus (‘ballooning’) reliably and accurately. Both are major etiological factors in the pathogenesis of pelvic organ prolapse and can be detected using equipment that is commonly available in O/G imaging departments. Women with avulsion and/ or major degrees of hiatal overdistension are at an increased risk of prolapse recurrence after reconstructive surgery. Identifying such pathology will not just allow a more realistic discussion of operative options, especially as regards mesh use, but has already opened up opportunities for entirely novel surgical approaches such as levator reconstruction and hiatal reduction. Most recently, translabial 4D imaging of the anal sphincter has made the assessment of anal incontinence simpler and less invasive. This technique will allow universal audits of of OASIS repair and eventually of obstetric management in general, enabling the introduction of ‘maternal birth trauma’ as a key performance indicator of obstetric services.

Oxidative status of cardinal ligament in pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common and distressing health problem in adult women, but the pathophysiological mechanism is yet to be fully elucidated. Previous studies have indicated that oxidative stress may be associated with POP. Thus, the aim of the present study was to investigate the oxidative status of pelvic supportive tissue in POP and further demonstrate that oxidative stress is associated with the pathogenesis of POP. A total of 60 samples were collected from females undergoing hysterectomy for POP or cervical intraepithelial neoplasia (CIN). This included 16 females with POP II, 24 females with POP III–IV (according to the POP-Q system) and 20 females with CIN II–III as the control group. Immunohistochemistry was utilized to measure the expression of oxidative biomarkers, 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE). Major antioxidative enzymes, mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx1) were measured through reverse transcription-quantitative polymerase chain reaction, western blotting and enzyme activity assays. The results demonstrated that in the cardinal ligament, the expression of 8-OHdG and 4-HNE was higher in the POP III–IV group compared with the POP II group and control group. The MnSOD and GPx1 protein level and enzyme activity were lower in the POP III–IV group compared with the POP II or the control group, while the mRNA expression level of MnSOD and GPx1 was increased. In conclusion, oxidative damage is increased in the pelvic supportive ligament of female patients with POP and the antioxidative defense capacity is decreased. These results support previous findings that oxidative stress is involved in the pathogenesis of POP.