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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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate translabial ultrasound (TLUS) parameters that may predict failed pessary fittings in women with symptomatic pelvic organ prolapse (POP)., Methods: All participants in this retrospective study presented to the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 seeking treatment for symptomatic POP. Each had chosen vaginal pessary as first-line treatment, undergoing TLUS in advance of placement. Participants were grouped by outcomes of pessary fittings as successful or failed. Group-wise demographic and clinical characteristics, including TLUS parameters, were then subjected to uni- and multi-variate logistic regression., Results: A total of 373 women qualified for analysis, 255 (68.4%) achieved success, and were fitted with acceptable pessaries. Predictors of failed fittings included younger age (61.54 ± 10.25 y vs 64.72 ± 10.30 y; P = 0.006), premenopausal status (14.4% vs 5.9%; P = 0.006), sizeable hiatal circumference (20.36 ± 2.33 cm vs 19.70 ± 2.50 cm; P = 0.02) and hiatal area (HA) (29.67 ± 7.14 cm2 vs 27.27 ± 6.99 cm2; P = 0.003), levator ani muscle (LAM) avulsion (odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.62-6.46; P = 0.001), enterocele (OR = 2.51, 95% CI = 1.11-5.68; P = 0.03), and the inferiormost aspect of cervix situated below symphysis pubis (OR = 0.52, 95% CI = 0.29-0.95; P = 0.03). In multivariate logistic regression, younger age (OR = 0.98, 95% CI = 0.95-1.00; P = 0.04), sizeable HA on Valsalva (OR = 1.04, 95% CI = 1.01-1.08; P = 0.02), LAM avulsion (OR = 2.87, 95% CI = 1.32-6.25; P = 0.008), and enterocele (OR = 2.70, 95% CI = 1.12-6.50; P = 0.03) emerged as independent predictors of failed pessary fittings., Conclusions: Younger age, LAM avulsion, enterocele, and sizeable HA on Valsalva proved independently predictive of failed pessary fittings in women with symptomatic POP., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)

Background: 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)., Materials and Methods: 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., Results: 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., Conclusion: 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., (© 2021 Japan Society of Obstetrics and Gynecology.)

Objective: To investigate clinical factors including translabial ultrasound parameters, which are predictive for choosing pessary type (Ring or Gellhorn) in the fitting trial, and to establish a predictive model., Methods: A retrospective study was conducted on symptomatic women with pelvic organ prolapse (POP) at the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 who were successfully fitted with pessaries. This retrospective study was supplemented with a prospective cohort study on women seeking pessary for first-line treatment of POP at the above tertiary center between December 2020 and April 2021 for validation. Enrolled participants were grouped by their fitted type of pessary. Demographic and clinical parameters between groups, including pelvic organ prolapse quantification and translabial ultrasound, were analyzed using logistic regression. A receiver operating characteristic curve was calculated using predictive values obtained by regression as the predictor for choosing pessary type in the pessary fitting trial., Results: The 181 participants included in the retrospective analysis were randomly divided into the "Development" and "Validation" datasets. In the "Development" set, multivariable logistic regression analyses showed that a younger age (odds ratio [OR]: 0.950; 95% confidence interval [CI]: 0.908-0.995; P = 0.026), a larger hiatal circumference on Valsalva (OR: 1.348; 95% CI: 1.103-1.647; P = 0.004), and a higher POP-Q stage (OR: 2.963; 95% CI: 1.210-7.255; P = 0.017) were independent predictors for successful fitting with the Gellhorn pessary. The predictive model was P = exp(Z)/[1 + exp(Z)], Z = -0.051 × Age (y) + 0.298 × hiatal circumference on Valsalva (cm) + 1.086 × pelvic organ prolapse stage (2, 3, or 4) - 5.490. The area under the receiver operating characteristic curves (AUC) was 0.776 (P < 0.001) and 0.705 (P < 0.001) based on the "Development" dataset and "Validation" datasets, respectively. The AUC was 0.815 (P < 0.001) based on the prospective cohort validation., Conclusions: For severe POP, women with younger age and larger hiatal circumference, Gellhorn pessaries should be their first choice instead of ring ones in pessary fitting trials., Competing Interests: Financial disclosures/conflicts of interest: None reported., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.)