Uterosacral Ligaments In Women Research Articles

Estrogen and Androgen Receptor Status in Uterosacral Ligaments of Women with Pelvic Organ Prolapse Stratified by the Pelvic Organ Prolapse Histology Quantification System

Menopause is a significant risk factor for pelvic organ prolapse (POP), suggesting that ovarian sex steroids play a major role in the etiology of the condition. POP results from failure of the uterine-cervix-vagina support structures, including the uterosacral ligament (USL). We previously identified consistent degenerative USL phenotypes that occur in POP and used their characteristics to develop a standardized POP Histologic Quantification System (POP-HQ). In this study, POP and matched control USL tissue was first segregated into the unique POP-HQ phenotypes, and specimens were then compared for estrogen receptor (ER) alpha (ERα), ERbeta (ERβ), the G-protein estrogen receptor (GPER), and androgen receptor (AR) content via immunohistochemical staining. ER and AR expression levels in the control USL tissues were indistinguishable from those observed in the POP-A phenotype, and partially overlapped with those of the POP-I phenotype. However, control-USL steroid receptor expression was statistically distinct from the POP-V phenotype. This difference was driven mainly by the increased expression of GPER and AR in smooth muscle, connective tissue, and endothelial cells, and increased expression of ERα in connective tissue. These findings support a multifactorial etiology for POP involving steroid signaling that contributes to altered smooth muscle, vasculature, and connective tissue content in the USL. Furthermore, these data support the concept that there are consistent and distinct degenerative processes that lead to POP and suggest that personalized approaches are needed that target specific cell and tissues in the pelvic floor to treat or prevent this complex condition.

Expression profile analysis of lncRNA and mRNA in uterosacral ligaments of women with pelvic organ prolapse by RNA-seq

Pelvic organ prolapse (POP) is a conventional gynecological condition and the mechanism is not entirely clear. Although an increasing number of studies revealed that long non-coding RNAs (lncRNAs) have essential functions in many diseases, little knowledge has been acquired in POP. The current study aimed to investigate the regulatory mechanism of lncRNA in POP. In this report, we investigated the expression profile of lncRNAs and mRNAs between POP and the control groups in human uterosacral ligament (hUSL) tissues through RNA-seq. Cytoscape was used to construct a POP-specific lncRNA-mRNA network and select key molecules. This RNA-Seq analysis uncovered a total of 289 lncRNAs, and 41 lncRNAs and 808 mRNAs were differentially expressed between the POP and non-POP groups. Four lncRNAs were identified and validated by real-time PCR. The result of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) indicated that differentially expressed lncRNAs were abundant in the biological processes and signaling pathways concerned in POP. The differentially expressed lncRNAs were mainly enriched in protein binding, the single-organism cellular process, and cytoplasmic part. The network was constructed based on the correlation analyses of the abnormally expressed lncRNAs and their target proteins to imitate their interactions. Taken together, this study was the first to demonstrate the differential expression profiles of lncRNA in POP and normal tissues by sequencing technology. Our study indicated that lncRNAs could correlate with the development of POP and may be as significant genes in the diagnosis and treatment of POP.

Using the novel pelvic organ prolapse histologic quantification system to identify phenotypes in uterosacral ligaments in women with pelvic organ prolapse

Pelvic organ prolapse is common, but the underlying etiologies are poorly understood, which limits our current prevention and treatment options. Our primary objective was to compare the uterosacral ligament histologic features in women with and without prolapse using the novel pelvic organ prolapse histologic quantification system. Our secondary aim was to determine whether composite histologic findings in uterosacral ligaments are associated with prolapse risk factors. This was a prospective cohort study in which paracervical uterosacral ligament biopsies were performed at the time of hysterectomy for primary prolapse or other benign gynecologic indications and processed for histologic evaluation. The pelvic organ prolapse quantification system was used to determine the prolapse stage. In this study, 9 prominent histologic features were semiquantitatively scored using the pelvic organ prolapse histologic quantification system in a blinded fashion and compared between prolapse and control groups. Unbiased principal component analysis of these scores was independently performed to identify potential relationships between histologic measures and prolapse risk factors. The histologic scores of 81 prolapse and 33 control ligaments were analyzed. Compared with the control group, women in the prolapse group were significantly older and more likely to be in the menopausal phase. There was no difference in the number of vaginal deliveries, body mass index, hormone use, or smoking status between the groups. To control for baseline differences, patients were also stratified by age over 40 years and menopausal status. Compared with the control group, the prolapse ligaments in the premenopausal group had significantly more loss of smooth muscle fibers within the fascicles (P<.001), increased inflammatory infiltrates of neutrophils within the tissue and perineural inflammatory cells (P<.01 and P=.04, respectively), and reduced neointimal hyperplasia (P=.02). Prolapse ligaments in the postmenopausal group exhibited elevated adipose content compared with that of the control group (P=.05). Amount of fibrillar collagen, total nonvascular smooth muscle, and muscle fiber vesicles of prolapse ligaments did not differ in either the premenopausal or postmenopausal group compared with that of the control group. Unbiased principal component analysis of the histologic scores separated the prolapse ligaments into 3 phenotypes: (1) increased adipose accumulation, (2) increased inflammation, and (3) abnormal vasculature, with variable overlap with controls. Posthoc analysis of these subgroups demonstrated a positive correlation between increasing number of vaginal deliveries and body mass index with increasing adipose content in the adipocyte accumulation and inflammatory phenotype and increasing neointimal hyperplasia in the vascular phenotype. However, only the relationship between vaginal delivery and adipocytes was significant in the adipose phenotype (R2=0.13; P=.04). Histologic phenotypes exist in pelvic support ligaments that can be distinguished using the pelvic organ prolapse histologic quantification system and principle component analysis. Vaginal delivery is associated with aberrant adipose accumulation in uterosacral ligaments. Our findings support a multifactorial etiology for pelvic organ prolapse contributing to altered smooth muscle, vasculature, and connective tissue content in crucial pelvic support structures. To confirm these associations and evaluate the biomechanical properties of histologic phenotypes of prolapse, larger studies are warranted. Closing this gap in knowledge will help optimize personalized medicine and help identify targets for prevention and treatment of this complex condition.

Expression of Heparanase in uterosacral ligaments of women with or without uterine prolapse

ObjectivePelvic organ prolapse (POP) is a global health problem for which the pathophysiological mechanism remains unclear. The loss of extracellular matrix proteins is considered an important molecular basis for this pathology. Heparanase is a heparin sulfate degrading endoglycosidase that has an important role in various biological processes and is a key component of extracellular matrix. The aim of this study was to compare expression of Heparanase in connective tissue of uterosacral ligaments in women with or without uterine prolapse. Study designThirty-nine women who underwent hysterectomy for benign reasons were enrolled in the study. Twenty-three women with uterine prolapse (stage ≥3) who underwent vaginal hysterectomy (VH) - POP group, were compared to sixteen women without uterine prolapse who underwent abdominal hysterectomy (stage <2) - control group. Uterosacral ligaments (USL) biopsies were obtained from all uterine specimens near their origin. All tissue samples were analyzed by immunohistochemistry and tested for the presence of Heparanase using antiheparanse antibody 733. ResultsHeparanse positive staining was more common in the connective tissue of uterosacral ligaments in women with uterine prolapse. Positive staining was seen in 17/23 (73.9 %) women with uterine prolapse compared to 4/16 (25 %) without uterine prolapse (p = 0.003). On multivariate logistic regression analysis, positive staining displayed a trend for an independent association with POP, after controlling for menopausal status and parity (OR 13.57, 95 %CI 0.82–224.4, p = 0.06). ConclusionHeparanase expression is more common in the connective tissue of uterosacral ligaments in women with uterine prolapse compared to women with no prolapse.

A pictorial guide to the ultrasound identification and assessment of uterosacral ligaments in women with potential endometriosis.

We believe the uterosacral ligaments (USLs) are an essential key to resolving the dilemma of diagnosing endometriosis non-invasively. This editorial will utilise laparoscopic and ultrasonographic figures and videos, along with written descriptive techniques, to educate clinicians, sonographers, sonologists and radiologists on normal and abnormal USLs to improve knowledge and skill in scanning patients with possible endometriosis.

Corrigendum] Genome‑wide DNA methylation analysis of uterosacral ligaments in women with pelvic organ prolapse

Following the publication of this paper, the authors have realized that the authors' address affiliation was not presented as it should have officially appeared. The address affiliation should have appeared as "Department of Gynecology" (not "Gynecology Department"), Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing. Therefore, the authors' affiliation address should have been written as follows: Lifang Zhang, Ping Zheng, Aihong Duan, Yan Hao, Chang Lu and Dan Lu. Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing100026, P.R.China. The authors confirm that there are no further errors in the study, and all the authors agree to this correction. The authors regret this error in the affiliation, and apologize for any inconvenience caused. [the original article was published in the Molecular Medicine Reports 19: 391‑399, 2019; DOI: 10.3892/mmr.2018.9656].

Genome‑wide DNA methylation analysis of uterosacral ligaments in women with pelvic organ prolapse.

Pelvic organ prolapse (POP) is an increasingly serious health problem that impairs quality of life and is caused by multiple additive genetic and environmental factors. As the uterosacral ligaments (ULs) provide primary support for the pelvic organs, it was hypothesized that disruption of these ligaments (as a result of aberrant methylation) may lead to a loss of support and eventually contribute to POP. In the present study, whether there are any aberrant methylations in the ULs of patients with POP compared to those of controls was investigated. Genomic DNA was isolated from the ULs of five women with POP and four women without POP, as controls, undergoing hysterectomy for benign conditions. An Illumina Infinium Methylation EPICBeadChips Infinium Human Methylation 850 K bead array was used to investigate the total methylation in the ULs. There were 3,723 differentially methylated CpG sites (Δβ<0.14; P<0.05), including 3,576 hypermethylation and 147 hypomethylation sites in the ULs of patients with POP compared with the normal controls. There were more hypermethylated CpG sites, but a high ratio of hypomethylation between CpG islands and the N-shelf; in the gene structure, there was more hypermethylation than hypomethylation in TSS1500 and the 5′ untranslated region. Gene ontology analysis demonstrated that these differentially methylated genes were associated with ‘cell morphogenesis’, ‘extracellular matrix’, ‘cell junction’, ‘protein binding’ and ‘guanosine triphosphatase activity’. Several significant pathways were identified, including ‘focal adhesion’ and ‘extracellular matrix-receptor interaction pathway’. This study provides evidence that there are differences in genome-wide DNA methylation between ULs in menopausal women with and without POP, and that epigenetic mechanisms may partly contribute to POP pathogenesis.

The increased of MMP-9 and MMP-2 with the decreased of TIMP-1 on the uterosacral ligament after childbirth.

IntroductionPelvic floor dysfunction is one of the causes of morbidity that have very active role in the degradation of collagen and elastin through an intermediary changes in matrix metalloproteinases (MMP) and its regulation. This research to evaluate level of MMP-9, MMP-2 and TIMP-1 expression on uterosacral ligament in women after vaginal delivery.MethodsThis research was conducted by collecting samples in consecutive sampling of biopsy uterosacral ligament from primigravida who underwent cesarean section because of obstructive labor at stage 1 and 2. As control, biopsy samples were taken from uterosacral ligament of primigravida a term who have not entered the labor phase and undergoing elective caesarean section surgery. The method in this study was cross sectional. The examination of MMP-9, MMP-2, and TIMP-1 expression by immunohistochemistry based on comparison of the sample and the control differences.ResultsThere are differences in the levels of Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and TIMP-1 in the uterosacral ligament of primigravida women in labor compared with women who are never in labor.ConclusionThere are increased levels of Matrix Metalloproteinase-9 and Matrix Metalloproteinase-2 with the decreased of TIMP-1 in the uterosacral ligament of primigravida women who underwent cesarean section because of obstructive labor at stage 1 and 2.

Expression of Tenascin in the Uterosacral Ligament is Stronger in Women with Pelvic Organ Prolapse

Objective: This study aimed to compare the expression of tenascin uterosacral ligament in women with and without pelvic organ prolapsen (POP).&#x0D; &#x0D; Methods: The research was carried out in Dr. Wahidin Sudirohusodo Hospital and other educational hospitals of obstetrics and gynecology division UNHAS Faculty of Medicine, which began on January 1st, 2011 until April 2012. This study assessed the expression of tenascin in 35 women with POP levels III and IV, and the controls&#x0D; were 35 women without POP. Tenascin expression was assessed by immunohistochemical examination using tenascin antibody staining (mouse monoclonal antibody Novacastra tenascin C, code NCL-Tenas C). The research was carried out cross sectional. Sampling was done by consecutive sampling. Data processed by the chi-square. The significance level used was 0.05.&#x0D; &#x0D; Results: The results showed that the characteristics of research subjects based on age, education, parity, labor history, history of big babies, not statistically significant. This indicates that the variable does not affect the calculation of the research data. While the characteristics&#x0D; of menopausal status and body mass index (BMI), from the&#x0D; analysis of risk factors for POP is associated significantly with a higher intensity of tenascin in post-menopausal status and BMI&gt; 25 (overweight) (p

Elastin Expression in Sacrouterina Ligament is Weaker in the Women with Pelvic Organ Prolapse

Objective: The research aims at comparing the elastin immunolabeling in the uterosacral ligaments in women with pelvic organ prolapse and without pelvic organ prolapse (POP).&#x0D; &#x0D; Methods: The research is done at Dr. Wahidin Sudirohusodo Hospital and education networking some hospitals the Obstetrics and Gynecological School of Medicine Hasanuddin University that began in January 2011 until April 2012. This research assessing expression of elastin on 35 women with a pop level III and IV and as control is 35 women without POP. Immunolabeling of elastin valued in staining checkings immunohistokimia uses antibodies elastin ( clone no. Ba-4 1:1600; Novacastra Laboratories Ltd, UK). The research was carried out by the cross sectional study. Mixed with chi-square. Level significance used is 0.05.&#x0D; &#x0D; Results: The results showed that the elastin immunolabeling in women with POP is decline on most sample expression with the intensity of elastin is weak (74.3%). The most control with the intensity of elastin immunolabeling is moderate (48.6%). Elastin immunolabeling seem significant in women with menopause and with BMI that overweight (all with p

MicroRNA-92 expression may be associated with reduced estrogen receptor β1 mRNA levels in cervical portion of uterosacral ligaments in women with pelvic organ prolapse

ObjectiveThis study examined microRNA-92 (miR-92) expression level in relation to the mRNA level of its potential target gene, estrogen receptor β1 (ERβ1), in female patients diagnosed with pelvic organ prolapse (POP). Study designBetween July 2012 and September 2014, a total of 104 patients were recruited at the First Affiliated Hospital of Sun Yat-sen University, which included 56 POP patients and 48 non-POP control subjects. Based on POP-Q score, the POP patients were further categorized into POP II and POP III groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify miR-92 expression level. ERβ1 tissue expression was measured by western blot and immunohistochemistry (IHC) methods. SPSS 19.0 software was used for statistical analysis. ResultsNo remarkable differences were observed between the POP group and non-POP group, and between the POP II and POP III groups, with respect to age, body mass index (BMI), parity, menopause status, and family history of POP. The expression level of miR-92 in the POP group was dramatically higher than the non-POP group (P<0.05). Consistent with the disease status, miR-92 expression level in POP III group was markedly higher than the POP II group (P<0.05). Western blot analysis revealed significantly reduced levels of ERβ1 in the POP group compared to the non-POP group, with similar results obtained between the POP III and POP II groups (all P<0.05). IHC results showed ERβ1 staining mainly in the nucleus and semi-quantitative measurements, expressed as positive expression rate, revealed that ERβ1 level in the POP group was clearly lower than non-POP group. Finally, statistical analysis of IHC results from uterosacral ligament tissue showed inverse correlation between miR-92 and ERβ1 expression levels in POP patients (P<0.05). ConclusionsOur results revealed increased miR-92 expression and decreased ERβ1 level in uterosacral ligaments of women diagnosed with POP, compared to non-POP subjects POP III patients exhibited more severe changes than POP II patients. Further, ERβ1expression is inversely correlated to miR-92 expression. Taken together, our results suggest that miR-92 and ERβ1 expression levels may be used as reliable diagnostic markers for assessing the severity of POP.

Sacrospinous hysteropexy versus vaginal hysterectomy with suspension of the uterosacral ligaments in women with uterine prolapse stage 2 or higher: multicentre randomised non-inferiority trial

Objective To investigate whether uterus preserving vaginal sacrospinous hysteropexy is non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments in the surgical treatment of uterine prolapse.Design Multicentre randomised controlled...

HOXA11 and MMP2 gene expression in uterosacral ligaments of women with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder that negatively impacts the quality of life in many women. Uterosacral ligaments (USLs) are supportive structures of the pelvic organs that are often attenuated in women with POP. The HOXA genes regulate the development of the uterosacral ligaments. We compared expression of HOXA11 and MMP2 in USLs of women with and without POP. A prospective sequential cross sectional study was conducted in ZTB Women's Health Research and Education Hospital. We compared expression of HOXA11 and MMP2 in USLs of women with (n:18) and without (n: 15) POP. Total RNA was isolated from patient (n:18) and control (n:15) uterosacral ligament tissues with TriPure isolation reagent according to the manufacturer's instructions. Expression levels of HOXA11 and MMP2 were determined using semiquantitative RT-PCR in a Light Cycler 480 system. Real-time ready catalog assays, which are short FAM-labeled hydrolysis probes containing locked nucleic acid, were used for RT-PCR reactions. There was no difference in patients' mean age, parity, body mass indexes, and menopausal status between two groups. Means of RNA expression of MMP2 were 1.27±0.6 and 0.75±0.4 in the POP group vs control group, respectively (p:0.007). Means of RNA expression of HOXA 11 were 2.57±2.4 and 1.94±1.4 in the POP group vs control group, respectively (p:0.376). The POP group was divided as mild and severe POP; there was no difference in HOXA11 and MMP2 RNA expression between groups (p>0.05). Although there was no difference HOXA11 RNA expression in USLs with the POP group vs control, there was a significant difference MMP2 RNA expression in USLs with the POP group vs control. There are limited studies on this subject, and study results are contradictory. Further investigations with larger numbers of cases are needed to clarify this subject.

Expression of matrix metalloproteinase-1 in round ligament and uterosacral ligament tissue from women with pelvic organ prolapse

To evaluate the matrix metalloproteinase-1 (MMP-1) expression in different parts of pelvic connective tissue in postmenopausal women with and without pelvic organ prolapse (POP). Ninety-one samples were obtained from only postmenopausal women (42 with POP and 49 non-POP subjects). All women were evaluated by pelvic organ prolapse quantitation. The POP group had stage 2 or more, and the controls had stage 1 or less. Round ligament (RL) and uterosacral ligament (USL) biopsies were obtained from women with POP and controls. Immunohistochemistry for MMP-1 was performed on formalin-fixed and paraffin-embedded sections. The two groups were matched for age, body mass index, parity and postmenopausal status. MedCalc Statistical Software Programme Version 12.0.5 was used for statistical analysis. Expression of MMP-1 were significantly higher in both RL and USL tissue from postmenopausal women with POP, compared with controls. MMP-1 immunoreactivities were identified in both RL and USL biopsies from all women with and without POP. The expression pattern of MMP-1 were similar in these ligaments and were significantly higher in POP group compared with control subjects. These changes indicate a possible relation between MMP-1 expression of RL and USL in women with and without POP.

Estrogen-related genome-based expression profiling study of uterosacral ligaments in women with pelvic organ prolapse

The aim of the study was to identify the differential expression of estrogen-related genes that may be involved in the menopause and pelvic organ prolapse (POP) using microarray analysis. An age, parity, and menopausal status-matched case-control study with 12 POP patients and 5 non-POP patients was carried out. The study was conducted from January to December 2010 at Yonsei University, Severance Hospital. We examined microarray gene expression profiles in uterosacral ligaments (USLs) from POP and non-POP patients. Total RNA was extracted from USL samples to generate labeled cDNA, which was hybridized to microarrays and analyzed for the expression of 44,049 genes. We identified differentially expressed genes and performed functional clustering. After clustering, we focused on transcriptional response and signal transduction gene clusters, which are associated with estrogen, and then validated the changes of gene expression levels observed with the microarray analysis using quantitative polymerase chain reaction (qPCR). The data from the microarray analysis using more than a 1.5-fold change with p value <0.05 resulted in 143 upregulated genes and 87 downregulated genes. Of 59 genes identified to be associated with signal transduction and transcription, 4 genes were chosen for qPCR that have been classified to be associated with estrogen. We found that estrogen receptor-related receptor-α (ERRα) was downregulated and that the expression of death-associated protein kinase 2 (DAPK 2), signal-transducing adaptor protein-2 (STAP-2), and interleukin (IL)-15 were upregulated. We found four differentially expressed genes by microarray analysis that may account for the way in which changes in estrogen level affect POP pathophysiology.

Involvement of Oxidative Stress and Mitochondrial Apoptosis in the Pathogenesis of Pelvic Organ Prolapse

Biomechanical weakness of the pelvic supportive structures has been proposed to be a cause of pelvic organ prolapse. However, the molecular mechanism involved in these changes is not completely understood. In this investigation we evaluated oxidative stress biomarkers in the uterosacral ligaments of women with pelvic organ prolapse and compared them with those of women with normal support. In addition, mitochondrial apoptosis was examined. Samples were collected from 26 women with advanced stage pelvic organ prolapse and 29 age matched controls. The expression levels of 8-OHdG and 4-hydroxy-2-nonenal in the uterosacral ligaments were measured using immunohistochemistry. To assess mitochondrial apoptosis we performed TUNEL assay, immunohistochemistry for cleaved caspase-3 and cytochrome c, and Western blot analyses for cleaved caspase-3 and caspase-9. The mean percentage of cells immunopositive for 8-OHdG, 4-hydroxy-2-nonenal, TUNEL, cleaved caspase-3 and cytochrome c in the uterosacral ligaments was significantly higher in patients with pelvic organ prolapse than in controls. Similarly, Western blot analysis revealed increased expression of cleaved caspase-3 and caspase-9 in patients with pelvic organ prolapse. Correlation analyses revealed significant positive correlations between the percentage of cells immunopositive for 8-OHdG or 4-hydroxy-2-nonenal and markers of mitochondrial apoptosis. Analyzing by pelvic organ prolapse quantification system stage according to C point, the mean percentage of cells immunopositive for 8-OHdG, 4-hydroxy-2-nonenal and cytochrome c was significantly higher in patients with pelvic organ prolapse compared to controls, regardless of stage. However, the mean percentage of TUNEL and cleaved caspase-3 positive cells was significantly higher only in patients with stage III or IV pelvic organ prolapse. Oxidative stress and increased mitochondrial apoptosis may contribute to the pathological process of pelvic organ prolapse.

Immunohistochemical analysis of connective tissue in patients with pelvic organ prolapse

The uterosacral ligaments are an important part of the pelvic support system. The objective of this study was to compare the expression of collagen type I and collagen type III in the uterosacral ligament biopsies from women with and without pelvic organ prolapse (POP). The uterosacral ligament biopsies were obtained from women with POP (n=29) and non-POP subjects (n=35). Immunohistochemistry for collagen type I and collagen type III was performed on formalin-fixed and paraffin-embedded sections. The two groups were matched for age, body mass index, parity and postmenopausal status. The expression of collagen type I (p<0.001) and collagen type III (p<0.0001) differed between women with POP and non-POP subjects. There was decreased expression of collagen type I and increased expression of collagen type III in uterosacral ligaments of women with POP compared with non-POP subjects. This difference indicates a possible relationship between POP and the immunohistochemical expression of collagen type I and collagen type III in uterosacral ligaments.

Increased microRNA-221/222 and decreased estrogen receptor α in the cervical portion of the uterosacral ligaments from women with pelvic organ prolapse

The aim of this study was to compare the expression of microRNA (miR)-221, miR-222, and estrogen receptor α (ERα) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP). Histologically confirmed full-thickness uterosacral ligament biopsies were procured during hysterectomies from 40 POP patients and 40 postmenopausal women without prolapse. Expression of miR-221/222 was determined by quantitative real-time polymerase chain reaction (PCR), and ERα protein expression was analyzed by Western blotting and immunohistochemistry. The mean expression levels of miR-221/222 both increased by approximately twofold in women with POP relative to controls, while ERα protein levels in POP patients were significantly lower than controls. Negative correlations were observed between ERα protein expression and both miR-221 (r = -0.8542) and miR-222 (r = -0.861) in POP patients. Elevated miR-221/222 expression levels are associated with, and may be responsible for, reduced ERα expression in the cervical portion of uterosacral ligaments of patients with POP. MiR-221/222 may serve as potential therapeutic targets for POP.

Decreased expression of elastin, fibulin‐5 and lysyl oxidase‐like 1 in the uterosacral ligaments of postmenopausal women with pelvic organ prolapse

Pelvic organ prolapse is associated with defects in connective tissues, including elastic fibers. The purpose of this study was to investigate the expression of fibulin-5 and lysyl oxidase-like 1 (LOXL1), which play an essential role in the synthesis and assembly of elastic fibers, in the uterosacral ligaments of women with advanced pelvic organ prolapse (POP) compared with controls. Specimens were obtained prospectively during transvaginal or abdominal hysterectomy from 30 women with advanced pelvic organ prolapse and 30 controls matched to the POP group for age and parity among postmenopausal women with benign gynecologic diseases. The expressions of elastin, fibulin-5 and LOXL1 in uterosacral ligaments were measured by immunohistochemistry. We detected a decreased, sometimes absent, expression of fibulin-5 and LOXL1 in the uterosacral ligaments of women with POP, despite a positive expression of elastin. There was a decrease in positive percentage of LOXL1 in the POP group (23.3%) compared with the controls (60%) (P = 0.004). With immunolabeling intensity classified as negative, weak, moderate or strong, there was a decrease in the expression of fibulin-5 in the POP group (P = 0.049). We also detected a significantly decreased expression of LOXL1 in the POP group (P = 0.001). There was decreased expression of fibulin-5 and LOXL1 in the uterosacral ligaments of patients with pelvic organ prolapse, while the elastin expression was equivalent, which may suggest the possibility of defects in elastic fiber remodeling in the postpartum period and contribute to POP.

Tissue Remodeling in the Female Reproductive Tract—A Complex Process Becomes More Complex: The Role of Hox Genes

Tissue Remodeling in the Female Reproductive Tract—A Complex Process Becomes More Complex: The Role of Hox Genes