Search

Introduction and Hypothesis: Vaginal delivery and resulting pelvic floor muscle (PFM) dysfunction are significant risk factors for pelvic floor dysfunction (PFD). Despite this, the biological basis underlying PFD after childbirth remain unclear. This study was aimed at assessing the early response of the vaginal wall and PFM to simulated birth injury (SBI) in rats., Methods: Forty female Sprague-Dawley rats were divided into four groups: control (sham operation), and 1, 4, and 14 days post-injury. In the SBI groups, a catheter was inserted into the vagina with 130 g of weight attached to the end, and the balloon was inflated to 5 ml for 2 h. Evaluation of vaginal tissues and PFMs included histological, immunohistochemical, Western blot, and uniaxial biomechanical testing., Results: In the vaginal wall, the SBI group showed significantly lower COL1A1 expression and higher MMP-2 and MMP-9 expression. At 4 and 14 days post-injury, there was a significant decrease in PFM fiber area and increased collagen content. The SBI group also exhibited significant increases in the expression of Nrf2, NQO1, HO-1, and SOD-2, indicating involvement of oxidative stress in both the vaginal wall and PFMs. Protein expression of Pax7 and MyoG, as well as the number of fibers with centralized nuclei, continued to increase significantly after SBI. Additionally, the vaginal wall of the SBI group showed a decreasing trend in tensile strength and elastic modulus, with a greater ultimate strain., Conclusion: Extracellular matrix remodeling, oxidative stress, decreased biomechanical properties, and muscle dysmyogenesis may collectively contribute to increased susceptibility to PFD development., (© 2024. The International Urogynecological Association.)

This study aimed to investigate the expression and significance of insulin-like growth factor binding protein 5 (IGFBP5) and extracellular matrix (ECM) related proteins in anterior vaginal wall tissues among aged pelvic organ prolapse (POP) patients. Tissues from the anterior vaginal wall were collected from 28 patients with POP and 20 patients without POP. The expression of protein and mRNA levels of IGFBP5 and ECM related proteins were evaluated in the vaginal wall tissues using immunohistochemistry, western blotting, and RT-qPCR techniques. The expression levels were then compared with clinical parameters. The expression levels of protein and mRNA of IGFBP5, collagen I, and collagen III were significantly lower in the POP group. Protein and mRNA expression levels of MMP2 were significantly higher in the POP group. IGFBP5 protein and mRNA expression levels were negatively correlated with age and significantly lower in older POP patients (≥ 65 years old) compared to younger POP patients (< 65 years old). IGFBP5 protein and mRNA expression levels were also significantly lower in POP-Q stage IV patients compared to POP-Q stage III patients. IGFBP5 expression level is negatively correlated with the age and severity of prolapse. The significant decrease in IGFBP5 expression may play a crucial part in the aging process and the occurrence of POP., (© 2024. The Author(s).)

Objective: Voiding Dysfunction (VD) is one of the most common disorders among women, which is characterized by a disorder in urination. Pelvic organ prolapse is one of the factors that can affect VD. In this study, the relationship between prolapse in the anterior, posterior, and apical areas and VD has been evaluated., Materials and Methods: This is a cohort retrospective study. The participants in this study were women with VD, who referred to the pelvic floor disorders clinic of Imam Khomeini Hospital in Tehran in 2018-2020. Clinical information was obtained retrospectively from the hospital's electronic data system, also symptoms (intermittent stream, incomplete voiding, poor flow, post void dribble, straining to void, stage anterior, posterior and apical) and urodynamic parameters (including EMG, PVR100, Qmax12, and pdet20) were evaluated, which included detailed questionnaires (Urinary Distress Inventory 6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7)), pelvic examination, and complete urodynamic evaluation., Results: There was a direct relationship between the age of the patients and the stage of prolapse (p<0.001). So that, the stage increased with age. In addition, it was found that the severity of urinary symptoms is related to the stage of prolapse in the apical area (p=0.001). Also, the results showed that intermittent stream symptoms and the symptoms of staining to void had a significant relationship with the stage of prolapse (III and IV) in the apical and anterior areas. Also, it was shown that only PVR > 100 had a significant relationship with the stage of prolapse in the apical area (p=0.001)., Conclusion: Intermittent stream and straining to void were related to the stages of prolapse in the apical and anterior regions. It was also concluded that the greater the prolapse, the higher the value of PVR > 100., Competing Interests: Conflict of Interests Authors declare no conflict of interests., (Copyright © 2024 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Introduction and Hypothesis: Collagen is a protein that confers robustness and resilience to several tissues. In the female reproductive system, collagen plays a critical role in maintaining the health and function of the vaginal walls. Aging leads to collagen reduction, which may cause vaginal dryness, irritation, and prolapse. We aim to analyze the structure and profile of collagen in the anterior vaginal wall of healthy pre-menopausal (pre-M) and post-menopausal (post-M) women under a scanning electron microscope (SEM)., Methods: Fragments of the anterior vaginal wall were collected and processed for light and scanning electron microscopy. Histological preparations were performed at first with Weigert's resorcin-fuchsin stain. Decellularized preparations were conducted, and the specimens were placed under an SEM to allow observation of the 3D organization of collagen., Results: Decellularized preparations of the pre-M specimens showed a vaginal wall with an irregular subepithelial layer, organized with ECM projections. The subepithelium evidenced the network of collagen fibrils, which seemed to support the epithelium as a basal layer. In specimens of post-M, a fusion of a network of fibrils from different direction axes was evidenced, with plate formation observed in the subepithelial plane, disfiguring the structural organization of fibrils., Conclusions: Older specimens showed a remodeling of collagen organization in comparison with younger samples of the anterior vaginal wall., (© 2023. The International Urogynecological Association.)

Purpose: Menopause is a risk factor for pelvic organ prolapse (POP) and is frequently associated with diminished vaginal wall support. To uncover relevant molecular mechanisms and provide potential therapeutic targets, we evaluated changes in the transcriptome and metabolome of the vaginal wall in ovariectomized rats to identify important molecular changes., Methods: Sixteen adult female Sprague-Dawley rats were randomly assigned to either the control or menopause group. Seven months after the operation, hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to observe changes in the rat vaginal wall structure. Differentially expressed genes (DEGs) and metabolites (DEMs) in the vaginal wall were detected by RNA-sequencing and LC-MS, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs and DEMs were performed., Results: We verified that long-term menopause causes vaginal wall injury by H&E and Masson trichrome staining. From the multiomics analyses, 20,669 genes and 2193 metabolites were identified. Compared with the control group, 3255 DEGs were found in the vaginal wall of long-term menopausal rats. Bioinformatics analysis showed that the DEGs were mainly enriched in mechanistic pathways, including cell-cell junction, extracellular matrix, muscle tissue developments, the PI3K-Akt signaling pathway, the MAPK signaling pathway, tight junctions and the Wnt signaling pathway. Additionally, 313 DEMs were found, and they consisted mostly of amino acids and their metabolites. DEMs were also enriched in mechanistic pathways, such as glycine, serine and threonine metabolism, glycerophospholipid metabolism, gap junctions and ferroptosis. Coexpression analysis of DEGs and DEMs revealed that biosynthesis of amino acids (isocitric acid and PKM ) and glycerophospholipid metabolism (1-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine and PGS1 ) are critical metabolic pathways, suggesting that POP induced by menopause may be associated with the regulation of these processes., Conclusion: The findings showed that long-term menopause greatly exacerbated vaginal wall support injury by decreasing the biosynthesis of amino acids and interfering with glycerophospholipid metabolism, which may result in POP. This study not only clarified that long-term menopause exacerbates damage to the vaginal wall but also provided insight into the potential molecular mechanisms by which long-term menopause induces POP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, He, Lin, Zheng, Zhang, Yu, Wang, Yang and Lin.)

Vaginal structural defects are involved in pelvic organ prolapse (POP). We tested whether mesenchymal stem cell (MSC) therapy can repair the weakened vaginal wall of POP patients as a novel POP treatment. Ninety-six ovariectomized rats were divided into 4 groups (n = 24/group): saline (sal), collagen (col), sal + MSC, and col + MSC groups. Two weeks after ovariectomy, rats received subepithelial injection of 0.3 ml saline, 0.3 ml collagen I gel, and 0.3 ml saline: 3 × 10 6 human umbilical cord mesenchymal stem cells (HUMSCs), or 0.3 ml collagen I gel: 3 × 10 6 HUMSCs into the anterior vaginal wall. Eight additional rats underwent in vivo bioluminescence imaging (BLI) to evaluate in vivo cell viability. The BLI signal disappeared within 1 week after MSC injection, and no in vivo MSC differentiation was found. Collagen I content was significantly lower at 4 and 12 weeks in the two MSC groups than in the sal and col groups, while collagen III was significantly higher (P < 0.001). The fraction of smooth muscle in the nonvascular muscularis increased significantly in the two MSC groups at 12 weeks (P < 0.001). ACTA2 mRNA in the col + MSC group was significantly higher than that in the sal group at 2 and 4 weeks (P = 0.042 and P = 0.040). mRNA levels of angiogenic factors (bFGF or VEGF) in the two MSC groups were significantly higher than those in the sal and col groups at different time points. HUMSCs normalized the fibromuscular structures of the vaginal wall of ovariectomized rats potentially through a paracrine effect., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brachytherapy is a common treatment in cervical, uterine and vaginal cancer management. The technique is characterised by rapid developments in the fields of medical imaging, dosimetry planning and personalised medical device design. To reduce unnecessary burden on patients, assessments and training of these technologies should preferable be done using high-fidelity physical phantoms. In this study, anthropomorphic deformable phantoms of the vaginal wall and cavity were developed for image-guided adaptive brachytherapy, in which vaginal wall biomechanics were mimicked. Phantoms were produced from both silicone and polyvinyl alcohol materials. Material characterisations were performed with uniaxial tensile tests, via which Young's moduli and toughness were quantified. In addition, the contrast between adjacent phantom layers was quantified in magnetic resonance images. The results showed that stress-strain curves of the silicone phantoms were within the range of those found in healthy human vaginal wall tissues. Sample preconditioning had a large effect on Young's moduli, which ranged between 2.13 and 6.94 MPa in silicone. Toughness was a more robust and accurate metric for biomechanical matching, and ranged between 0.23 and 0.28 ·10 6 J·m -3 as a result of preconditioning. The polyvinyl alcohol phantoms were not stiff or tough enough, with a Young's modulus of 0.16 MPa and toughness of 0.02 ·10 6 J·m -3 . All materials used could be clearly delineated in magnetic resonance images, although the MRI sequence did affect layer contrast. In conclusion, we developed anthropomorphic deformable phantoms that mimic vaginal wall tissue and are well visible in magnetic resonance images. These phantoms will be used to evaluate the properties and to optimise the development and use of personalised brachytherapy applicators., (Creative Commons Attribution license.)

Vaginal atrophy caused by the aging process and perineal trauma has a negative impact on women. A new vaginal atrophy treatment is injection of materials into the vaginal wall, including platelet-rich plasma (PRP), autogenous fat graft (AFG), hyaluronic acid (HA), botulinum toxin (BTX), and collagen, but to date their efficacy has not been reviewed. Vaginal wall injection is available only for mild cases of vaginal atrophy or as an adjunct to vaginal surgery. PRP is used mainly to restore vaginal function, and multiple injections are needed to achieve good results in vaginal atrophy. HA, AFG, and collagen are used mainly to augment the vaginal wall. BTX injection can inhibit vaginal muscle spasm and reduce pain during sexual intercourse in patients with vaginismus. Injection of most of these materials into vaginal wall is effective and relatively safe. Vascular embolisms are the most serious complication of vaginal injection and should be prevented. In addition, there has been no randomized double-blind placebo-controlled trial or discussion of methods to avoid serious complications resulting from vaginal injection. Therefore, further studies of the injection of materials into the vaginal wall to treat vaginal atrophy are required, and the procedures should be standardized to benefit more patients.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Large vaginal cysts during pregnancy are rare and can mislead Obstetricians to a false diagnosis, that of "Protruding membranes". Aspiration of the cyst can be easily performed, resulting in the collapsing of the cyst and an uneventful vaginal delivery can be conducted., Competing Interests: None declared.

An optical probe was developed to measure the change of oxy-hemoglobin (OHb), deoxy- hemoglobin (RHb), and total hemoglobin (THb) along with temperature from the vaginal wall of female rats. Apomorphine (APO, 80 μg/kg) was administered to elicit sexual arousal in female Sprague Dawley rats (SD, 180-200 g). The behavior changes caused by APO administration were checked before monitoring vaginal responses. The changes of oxy-, deoxy-, and total hemoglobin concentration and the temperature from the vaginal wall were monitored before, during, and after APO administration. Animals were under anesthesia during the measurement. After APO administration, the concentration of OHb (55 ± 29 μM/DPF), RHb (33 ± 25 μM/DPF), and THb (83 ± 59 μM/DPF) in the vaginal wall increased in a few min, while saline administration did not cause any significant change. In case of the vaginal temperature change, APO decreased the temperature slightly in the vaginal wall while saline administration did not show any temperature change in the vaginal wall. As the outcomes demonstrated, the developed probe can detect hemodynamic and temperature variation in the vaginal wall. The hemodynamic information acquired by the probe can be utilized to establish an objective and accurate standard of female sexual disorders.

Although the underlying mechanisms of pelvic organ prolapse (POP) remain unknown, disruption of elastic fiber metabolism within the vaginal wall extracellular matrix (ECM) has been highly implicated. It has been hypothesized that elastic fiber fragmentation correlates to decreased structural integrity and increased risk of prolapse; however, the mechanisms by which elastic fiber damage may contribute to prolapse are poorly understood. Furthermore, the role of elastic fibers in normal vaginal wall mechanics has not been fully ascertained. Therefore, the objective of this study is to investigate the contribution of elastic fibers to murine vaginal wall mechanics. Vaginal tissue from C57BL/6 female mice was mechanically tested using biaxial extension-inflation protocols before and after intraluminal exposure to elastase. Elastase digestion induced marked changes in the vaginal geometry, and biaxial mechanical properties, suggesting that elastic fibers may play an important role in vaginal wall mechanical function. Additionally, a constitutive model that considered two diagonal families of collagen fibers with a slight preference toward the circumferential direction described the data reasonably well before and after digestion. The present findings may be important to determine the underlying structural and mechanical mechanisms of POP, and aid in the development of growth and remodeling models for improved assessment and prediction of changes in structure-function relationships with prolapse development., (Copyright © 2019 by ASME.)