Mechanisms governing protective pregnancy-induced adaptations of the pelvic floor muscles in the rat preclinical model.
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ABSTRACT:
SUBMITTER: Rieger MM
PROVIDER: S-EPMC9172206 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Mechanisms governing protective pregnancy-induced adaptations of the pelvic floor muscles in the rat preclinical model.
Rieger Mary M MM Wong Michelle M Burnett Lindsey A LA Sesillo Francesca Boscolo FB Baynes Brittni B BB Alperin Marianna M
American journal of obstetrics and gynecology 20211118 5
<h4>Background</h4>The intrinsic properties of pelvic soft tissues in women who do and do not sustain birth injuries are likely divergent. However, little is known about this. Rat pelvic floor muscles undergo protective pregnancy-induced structural adaptations-sarcomerogenesis and increase in intramuscular collagen content-that protect against birth injury.<h4>Objective</h4>We aimed to test the following hypotheses: (1) the increased mechanical load of a gravid uterus drives antepartum adaptatio ...[more]
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Project description:BackgroundVaginal childbirth is a key risk factor for pelvic floor muscle injury and dysfunction, and subsequent pelvic floor disorders. Multiparity further exacerbates these risks. Using the rat model, validated for the studies of the human pelvic floor muscles, we have previously identified that a single simulated birth injury results in pelvic floor muscle atrophy and fibrosis.ObjectiveTo test the hypothesis that multiple birth injuries would further overwhelm the muscle regenerative capacity, leading to functionally relevant pathological alterations long-term.Study designSprague-Dawley rats underwent simulated birth injury and were allowed to recover for 8 weeks before undergoing additional birth injury. Animals were sacrificed at acute (3 and 7 days postinjury), subacute (21, 28, and 35 days postinjury), and long-term (8 and 12 weeks postinjury) time points post second injury (N=3-8/time point), and the pubocaudalis portion of the rat levator ani complex was harvested to assess the impact of repeated birth injuries on muscle mechanical and histomorphological properties. The accompanying transcriptional changes were assessed by a customized NanoString panel. Uninjured animals were used as controls. Data with a parametric distribution were analyzed by a 2-way analysis of variance followed by post hoc pairwise comparisons using Tukey's or Sidak's tests; nonparametrically distributed data were compared with Kruskal-Wallis test followed by pairwise comparisons with Dunn's test. Data, analyzed using GraphPad Prism v8.0, San Diego, CA, are presented as mean ± standard error of the mean or median (range).ResultsFollowing the first simulated birth injury, active muscle force decreased acutely relative to uninjured controls (12.9±0.9 vs 25.98±2.1 g/mm2, P<.01). At 4 weeks, muscle active force production recovered to baseline and remained unchanged at 8 weeks after birth injury (P>.99). Similarly, precipitous decrease in active force was observed immediately after repeated birth injury (18.07±1.2 vs 25.98±2.1 g/mm2, P<.05). In contrast to the functional recovery after a single birth injury, a long-term decrease in muscle contractile function was observed up to 12 weeks after repeated birth injuries (18.3±1.6 vs 25.98±2.1 g/mm2, P<.05). Fiber size was smaller at the long-term time points after second injury compared to the uninjured group (12 weeks vs uninjured control: 1485 (60.7-5000) vs 1989 (65.6-4702) μm2, P<.0001). The proportion of fibers with centralized nuclei, indicating active myofiber regeneration, returned to baseline at 8 weeks post-first birth injury, (P=.95), but remained elevated as far as 12 weeks post-second injury (12 weeks vs uninjured control: 7.1±1.5 vs 0.84±0.13%, P<0.0001). In contrast to the plateauing intramuscular collagen content after 4 weeks post-first injury, fibrotic degeneration increased progressively over 12 weeks after repeated injury (12 weeks vs uninjured control: 6. 7±1.1 vs 2.03±0.2%, P<.001). Prolonged expression of proinflammatory genes accompanied by a greater immune infiltrate was observed after repeated compared to a single birth injury.ConclusionOverall, repeated birth injuries lead to a greater magnitude of pathological alterations compared to a single injury, resulting in more pronounced pelvic floor muscle degeneration and muscle dysfunction in the rat model. The above provides a putative mechanistic link between multiparity and the increased risk of pelvic floor dysfunction in women.
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Project description:Upload 2. Test data from multiple pelvic floor muscles from rats. Data was acquired using a Bruker Maxis Impact and C18 RP-UHPLC. Positive polarity acquisition of LC-MS/MS.
2020-11-25 | MSV000086522 | GNPS
Project description:ObjectiveExcessive pelvic floor muscle activity has been suggested as a source of pain in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Our objective was to determine whether men with CP/CPPS have changes in neural drive that impair their ability to relax pelvic floor muscles.MethodsWe recruited 90 men (42 with CP/CPPS and 48 in the control group [without a history of pelvic pain]). All completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We quantified the ability to relax by comparing resting pelvic floor muscle activity under 2 conditions: a "rest-only" condition, in which participants were instructed to simply relax, and a "rest-between-contraction" condition, in which participants were instructed to rest for several seconds between voluntary pelvic floor muscle contractions. We used multivariate mixed-effects models to examine differences between the groups (men with CP/CPPS and men in the control group) as well as the effect of 6 symptoms captured by the NIH-CPSI: pain related to location (perineum, testicles, penis, suprapubic region) and activity (urination, ejaculation).ResultsMen with CP/CPPS were significantly different from men in the control group; men with CP/CPPS had higher resting activity in the rest-between-contraction condition than in the rest-only condition, whereas men in the control group had similar resting activities in both conditions. This effect was strongest in men who reported ejaculation-related pain, which was 70% of the CP/CPPS group.ConclusionMen without a history of pelvic pain were able to relax their pelvic floor muscles back to baseline after performing voluntary pelvic floor muscle contractions. In contrast, men with CP/CPPS, particularly those with ejaculation-related pain, had an impaired ability to relax their pelvic floor muscles.ImpactThis study may support the investigation of more personalized physical therapist approaches for CP/CPPS that enhance the ability to relax pelvic floor muscles as a mechanism for pain reduction.
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Project description:PurposePostoperative recovery of urinary continence has a great impact on quality of life for patients undergoing robot-assisted radical prostatectomy (RARP). A variety of surgical techniques including reconstruction of the periurethral structure have been introduced, and yet there are no effective methods that promote early urinary continence recovery after surgery. We hypothesized that the preservation of pelvic floor muscle structure could be responsible for early recovery of urinary continence after surgery.MethodsA total of 94 consecutive patients who underwent RARP at our hospital were enrolled in this study. Operative video records were reviewed and the severity of pelvic floor muscle injury was classified according to the scoring system that we devised in this study. Briefly, damage of pelvic floor muscles was classified into 4 categories; intact, fascial injury, unilateral muscle injury, and bilateral muscle injury. The volume of urinary incontinence was measured for 2 days after removal of the urethral catheter, and the incontinence ratio (amount of incontinence/total volume of urine per day) was calculated. Predictive factors for immediate incontinence after catheter removal were identified by multivariate regression analysis.ResultsThe severity of puboperineal muscle injury was significantly associated with the early incontinence ratio after catheter removal (p < 0.001). Age at surgery and severity of puboperineal muscle injury were independent predictors for early incontinence after catheter removal.ConclusionPreservation of the pelvic floor muscle, particularly the puboperineal muscle is an important factor for early continence recovery after RARP.
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Project description:Chronic pelvic pain (CPP) is a complex condition with a high economic and social burden. Although it is usually treated with botulinum neurotoxin type A (BoNT/A) injected into the pelvic floor muscles (PFM), its effect on their electrophysiological condition is unknown. In this study, 24 CPP patients were treated with BoNT/A. Surface electromyographic signals (sEMG) were recorded at Weeks 0 (infiltration), 8, 12 and 24 from the infiltrated, non-infiltrated, upper and lower PFM. The sEMG of 24 healthy women was also recorded for comparison. Four parameters were computed: root mean square (RMS), median frequency (MDF), Dimitrov's index (DI) and sample entropy (SampEn). An index of pelvic electrophysiological impairment (IPEI) was also defined with respect to the healthy condition. Before treatment, the CPP and healthy parameters of almost all PFM sides were significantly different. Post-treatment, there was a significant reduction in power (<RMS), a shift towards higher frequencies (>MDF), lower fatigue index (<DI) and increased information complexity (>SampEn) in all sites in patients, mainly during PFM contractions, which brought their electrophysiological condition closer to that of healthy women (<IPEI). sEMG can be used to assess the PFM electrophysiological condition of CPP patients and the effects of therapies such as BoNT/A infiltration.
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Project description:BackgroundWearing high-heeled shoes is a common phenomenon among women. However, the association between wearing high heels and pelvic floor function is largely unknown. Our aim was to evaluate the effects of wearing different height shoes on pelvic floor function and to analyze the influencing factors.MethodsThis was a population-based, cross-sectional study performed in general hospitals with a pelvic floor subspecialty in some cities of China. All participants completed a Urogenital Distress Inventory (UDI-6) questionnaire that consisted of demographic data, information about wearing shoes, and information about pelvic floor function (UDI-6). One-way ANOVA was carried out to compare the differences among 4 groups according to the heel height (<3, 3-5, 5-7, and >7 cm groups). Multivariate logistic regression was performed to identify the factors influencing the effect of wearing 3-5 cm high-heeled shoes on pelvic floor function.ResultsIn total, 1,263 participants finished the questionnaire and full data were collected. The 4 groups were comparable for clinical data, and participants who wore 3-5 cm high-heeled shoes had the lowest UDI-6 scores. Multivariate analysis revealed that the number of hours (≥8 h) wearing high heels per day and the thickness diameter (≥3 cm) of the heel were important factors affecting the protective effect of wearing 3-5 cm high-heeled shoes on pelvic floor function.ConclusionsWearing heeled shoes with a 3-5 cm heel height and ≥3 cm thickness for a long period of time is good for the pelvic floor function of women.
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Project description:Age-related pelvic floor muscle (PFM) dysfunction is a critical defect in the progression to pelvic floor disorders (PFDs). Despite dramatic prevalence of PFDs in older women, the underlying pathophysiology of age-related PFM dysfunction remains poorly understood. Using cadaveric specimens, we quantified aging effects on functionally relevant PFM properties and compared PFMs with the appendicular muscles from the same donors. PFMs, obturator internus, and vastus lateralis were procured from younger (N = 4) and older (N = 11) donors with known obstetrical and medical history. Our findings demonstrate that PFMs undergo degenerative, rather than atrophic, alterations. Importantly, age-related fibrotic degeneration disproportionally impacts PFMs compared to the appendicular muscles. We identified intramuscular lipid accumulation as another contributing factor to the pathological alterations of PFMs with aging. We observed a fourfold decrease in muscle stem cell (MuSC) pool of aged relative to younger PFMs, but the MuSC pool of appendicular muscles from the same older donors was only twofold lower than in younger group, although these differences were not statistically significant. Age-related degeneration appears to disproportionally impact PFMs relative to the appendicular muscles from the same donors. Knowledge of tissue- and cell-level changes in aged PFMs is essential to promote our understanding of the mechanisms governing PFM dysfunction in older women.
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Project description:BackgroundThe mechanisms of the microenergy acoustic pulse (MAP) therapy on restoring structure and function of pelvic floor muscles (PFM) after simulated birth injury are not well understood.MethodsA total 24 female Sprague-Dawley rats were randomly grouped into sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + β-aminopropionitrile (BAPN, an irreversible LOX inhibitor), and VBDO + BAPN and treated with MAP (n=6 in each group). The MAP therapy was administered 2 times per week for 4 weeks with 1-week washout, the functional and histological studies were conducted in all 24 rats. The viscoelastic behavior of the PFM, including iliococcygeus (IC) and pubococcygeus (PC), was examined with a biomechanical assay. The structure of the PFM was assessed by immunofluorescence and Masson's trichrome staining.ResultsThe leak point pressure (LPP) assay demonstrated that the MAP therapy group had higher LPPs compared to that of VBDO and BAPN groups. In the sham group, the muscular stiffness (K) of IC muscle was significantly higher than that of PC muscle while the pelvic floor muscle rebound activity (MRA) of PC muscle was stronger than that of IC muscle (291.26±45.33 and 241.18±14.23 N/cm2, respectively). Both VBDO and BAPN decreased the MRA and increased the K in both IC and PC. Histologic examination revealed increased fibrous tissue (collagen) and degeneration of muscle fibers in both VBDO and BAPN groups. MAP therapy significantly reduced the collagen content and improved the architecture of muscle fibers.ConclusionsMAP appears to restore the structure and function of PFM by regenerating muscular fibers and improving biomechanical properties in an animal model of simulated birth injury.
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Project description:To identify the functional correlation of overactive pelvic floor muscles (OPFM) with cystoscopic and fluoroscopic urodynamic studies (FUDS), including urethral pressure measurements.Patients refractory to conservative therapy including bladder retraining, medications and pelvic muscle exercises for a variety of gamut of storage and voiding disorders were evaluated. Prospective data for 201 patients across both genders who underwent flexible cystoscopy and urodynamics for lower urinary tract symptoms (LUTS) refractory to conservative management between 01 Jan 2014 and 01 Jan 2016 was collected. Factors studied included history of LUTS, voiding patterns, physical examination, cystoscopic findings and functional studies, with maximum urethral closing pressure (MUCP).A total of 201 were patients recruited. The 85 were diagnosed with OPFM based on clinical presentation and presence of pelvic floor tenderness on examination. Significant differences were noted on functional studies with FUDS and urethral pressure measurement. Subjects with pelvic floor tenderness were found to have a higher (MUCP) at 93.1 cm H2O compared to 80.6 cm H2O (P=0.015).There are distinct characteristics of OPFM on clinical examination and functional studies, in particular MUCP. In patients refractory to conservative treatments, specific urodynamics tests are useful in sub-categorising patients. When OPFM is diagnosed, the impact on patient management is significant, and targeted intervention with pelvic floor physiotherapy is central in the multimodal approach of this complex condition.
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Project description:ObjectiveTo evaluate and compare the efficacy and safety of Botulinum Toxin A (BTA) injections versus placebo injections, combined with pelvic floor muscle therapy (PFMT), in women with chronic pelvic pain (CPP).DesignRandomised, double-blinded clinical trial (January 2020-April 2023).SettingThis multicentre study was conducted at four hospitals in the Netherlands.Population and sampleNinety-four women with CPP and increased pelvic floor muscle tone despite previous PFMT, were enrolled.MethodsParticipants received either BTA injections (100 units) or placebo injections into the pelvic floor muscle, followed by four PFMT sessions.Main outcomes and measuresPrimary outcomes included the number of women with at least a 33% reduction in pain and those reporting (very) much improvement of their pain. Secondary outcomes covered quality of life and pelvic floor function. Follow-up visits were scheduled at 4, 8, 12, and 26 weeks post-treatment. Mixed models for repeated measurements were used for analysis.ResultsA 33% reduction or more in average pain score was reported by 15 participants (33%) after BTA treatment and 9 participants (20%) after placebo treatment (odd ratio placebo/BTA 1.88; 95% CI 0.72-4.90, p = 0.19). In both groups, 8 women (17%) reported their improvement as (very) much better (odd ratio placebo/BTA 0.947; 95% CI 0.32-2.80, p = 0.92). Pelvic floor resting activity decreased significantly after BTA treatment compared to placebo (p = 0.001).ConclusionThe results from this study do not support the use of BTA injections in the management of CPP in women.
| S-EPMC11704059 | biostudies-literature