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Impact of parturition on chemokine homing factor expression in the vaginal distention model of stress urinary incontinence.

ABSTRACT: Human childbirth simulated by vaginal distention is known to increase the expression of chemokines and receptors involved in stem cell homing and tissue repair. We hypothesized that pregnancy and parturition in rats contributes to the expression of chemokines and receptors after vaginal distention.We used 72 age matched female Lewis rats, including virgin rats with and without vaginal distention, and delivered rats with and without vaginal distention. Each rat was sacrificed immediately, or 3 or 7 days after vaginal distention and/or parturition, and the urethra was harvested. Relative expression of chemokines and receptors was determined by real-time polymerase chain reaction. Mixed models were used with the Bonferroni correction for multiple comparisons.Vaginal distention up-regulated urethral expression of CCL7 immediately after injury in virgin and postpartum rats. Hypoxia inducible factor-1? and vascular endothelial growth factor were up-regulated only in virgin rats immediately after vaginal distention. CD191 expression was immediately up-regulated in postpartum rats without vaginal distention compared to virgin rats without vaginal distention. CD195 was up-regulated in virgin rats 3 days after vaginal distention compared to virgin rats without vaginal distention. CD193 and CXCR4 showed delayed up-regulation in virgin rats 7 days after vaginal distention. CXCL12 was up-regulated in virgin rats 3 days after vaginal distention compared to immediately after vaginal distention. Interleukin-8 and CD192 showed no differential expression.Vaginal distention results in up-regulation of the chemokines and receptors expressed during tissue injury, which may facilitate the spontaneous functional recovery previously noted. Pregnancy and delivery up-regulated CD191 and attenuated the expression of hypoxia inducible factor-1? and vascular endothelial growth factor in the setting of vaginal distention, likely by decreasing hypoxia.

SUBMITTER: Lenis AT

PROVIDER: S-EPMC4383296 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Impact of parturition on chemokine homing factor expression in the vaginal distention model of stress urinary incontinence.

Lenis Andrew T AT Kuang Mei M Woo Lynn L LL Hijaz Adonis A Penn Marc S MS Butler Robert S RS Rackley Raymond R Damaser Margot S MS Wood Hadley M HM

The Journal of urology 20120925 4

<h4>Purpose</h4>Human childbirth simulated by vaginal distention is known to increase the expression of chemokines and receptors involved in stem cell homing and tissue repair. We hypothesized that pregnancy and parturition in rats contributes to the expression of chemokines and receptors after vaginal distention.<h4>Materials and methods</h4>We used 72 age matched female Lewis rats, including virgin rats with and without vaginal distention, and delivered rats with and without vaginal distention ...[more]

PMID: 23022009

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Project description:BACKGROUND:The molecular mechanisms underlying stress urinary incontinence (SUI) at the tissue level are poorly understood. OBJECTIVE:To study genetic and molecular alterations in the urethras of animals with experimentally induced SUI. DESIGN, SETTING, AND PARTICIPANTS:Cohort analysis of primiparous 2-month-old female Sprague-Dawley rats with experimentally induced SUI versus those who did not develop SUI in a university research laboratory setting. INTERVENTION:Rats underwent intravaginal balloon dilation within 24 hours of parturition followed by bilateral ovariectomy one week later. Transvesical cystometry was performed 12 weeks after parturition. Rats were classified as continent (C) or incontinent (I) according to the results of cystometry. MEASUREMENTS:The expression of over 22,000 genes in urethral tissue from the two groups was assessed with the use of an oligo microarray. The expression of relevant genes was confirmed by real-time polymerase chain reaction. Protein expression of small mothers against decapentaplegic 2 (Smad2), one of the differentially expressed genes, was extensively studied by immunohistochemistry and Western blot analysis. Regulation of Smad2 activity by transforming growth factor-beta (TGF-beta) was assessed in cultured urethral smooth muscle cells (USMCs). RESULTS AND LIMITATIONS:After intervention, 14 (58.3%) rats remained continent and 10 (41.7%) became incontinent. There were significant differences in the expression of 42 urethral genes between continent and incontinent rats. The expression of genes involved in the TGF cellular signaling pathway (Smad2), collagen breakdown (matrix metalloproteinase 13 [Mmp13]), and smooth muscle inhibition (regulator of G-protein signaling 2 [Rgs2]) was significantly increased in the incontinent group. SMAD2 protein expression was significantly upregulated in the incontinent rats. In cultured USMCs, SMAD2 phosphorylation and nuclear translocation increased after Tgf-beta treatment. CONCLUSIONS:Genes important in inflammation, collagen breakdown, and smooth muscle inhibition are upregulated in the urethras of female rats with parturition-associated incontinence.

Project description:BackgroundLittle is known about short- and long-term pain and functional activity after surgery for pelvic organ prolapse.ObjectiveThe objectives of the study were to describe postoperative pain and functional activity after transvaginal native tissue reconstructive surgery with apical suspension and retropubic synthetic midurethral sling and to compare these outcomes between patients receiving 2 common transvaginal prolapse repairs, uterosacral ligament, and sacrospinous ligament vaginal vault suspension.Study designThis planned secondary analysis of a 2 × 2 factorial randomized trial included 374 women randomized to receive uterosacral (n = 188) or sacrospinous (n = 186) vaginal vault suspension to treat both stages 2-4 apical vaginal prolapse and stress urinary incontinence between 2008 and 2013 at 9 medical centers. Participants were also randomized to receive perioperative pelvic muscle therapy or usual care. All patients received transvaginal native tissue repairs and a midurethral sling. Participants completed the Surgical Pain Scales (0-10 numeric rating scales; higher scores = greater pain) and Activity Assessment Scale (0-100; higher score = higher activity) prior to surgery and at 2 weeks, 4-6 weeks, and 3 months postoperatively. The MOS 36-item Short-Form Health Survey was completed at baseline and 6, 12, and 24 months after surgery; the bodily pain, physical functioning, and role-physical subscales were used for this analysis (higher scores = less disability). Self-reported pain medication use was also collected.ResultsBefore surgery, average pain at rest and during normal activity were (adjusted mean ± SE) 2.24 ± 0.23 and 2.76 ± 0.25; both increased slightly from baseline at 2 weeks (+0.65, P = .004, and +0.74, P = .007, respectively) and then decreased below baseline at 3 months (-0.87 and -1.14, respectively, P < .001), with no differences between surgical groups. Pain during exercise/strenuous activity and worst pain decreased below baseline levels at 4-6 weeks (-1.26, P = .014, and -0.95, P = .002) and 3 months (-1.97 and -1.50, P < .001) without differences between surgical groups. Functional activity as measured by the Activity Assessment Scale improved from baseline at 4-6 weeks (+9.24, P < .001) and 3 months (+13.79, P < .001). The MOS 36-item Short-Form Health Survey Bodily Pain, Physical Functioning, and Role-Physical Scales demonstrated significant improvements from baseline at 6, 12, and 24 months (24 months: +5.62, +5.79, and +4.72, respectively, P < .001 for each) with no differences between groups. Use of narcotic pain medications was reported by 14.3% of participants prior to surgery and 53.7% at 2 and 26.1% at 4-6 weeks postoperatively; thereafter use was similar to baseline rates until 24 months when it decreased to 6.8%. Use of nonnarcotic pain medication was reported by 48.1% of participants prior to surgery, 68.7% at 2 weeks, and similar to baseline at 3 months; thereafter use dropped steadily to 26.6% at 2 years. Uterosacral ligament suspension resulted in less new or worsening buttock pain than sacrospinous suspension at 4-6 weeks postoperatively (4.6% vs 10.5%, P = .043) but no difference in groin or thigh pain.ConclusionPain and functional activity improve for up to 2 years after native tissue reconstructive surgery with uterosacral or sacrospinous vaginal vault suspension and midurethral sling for stages 2-4 pelvic organ prolapse. On average, immediate postoperative pain is low and improves to below baseline levels by 4-6 weeks.

Project description:ContextStress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain.ObjectiveTo investigate the long-term impact of delivery mode on SUI and UUI.Evidence acquisitionWe searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI ≥1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias.Evidence synthesisPooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56-2.19; I(2)=57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p=0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84-1.45; I(2)=50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02-1.65; I(2)=37%; risk difference: 2.6%).ConclusionsCompared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%.Patient summaryIn this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency.

Project description:ObjectiveThe study aimed to evaluate the contributions of levator ani muscle (LAM) injury, vesical neck movement, urethral length and mobility, and urethral sphincter dysfunction observed on magnetic resonance imaging (MRI) towards stress urinary incontinence (SUI) after vaginal delivery.Materials and methodsFifty primiparous women after 6 months of delivery (15 with SUI and 35 without) and 35 nulliparous as continent controls underwent MRI at rest and Valsalva maneuver. A published levator ani scoring system was used to characterize morphological changes of LAM. The severity of the injury was divided into three categories as none, minor, and major. A series of common parameters including levator plate angle, iliococcygeal angle, and levator hiatus were used to describe the functional conditions of LAM. Urethral mobility was defined based on the rotation of the urethra between Valsalva and rest status. Vesical neck movement was evaluated by its distance to the pubococcygeal line. Urethral sphincter dysfunction was defined as the widening of the proximal urethra and/or funneling at the urethrovesical junction during Valsalva.ResultsPrimiparous incontinent (PI) women had additional major levator ani defects (33.3% vs. 17.1%) while less minor defects (0.7% vs. 31.4%) than primiparous continent (PC) women. Vesical neck downward movement in PI women was more obvious than PC women (28.5 mm vs. 24.2 mm, p = 0.006). Urethral mobility was more active in primiparous women than in nulliparous continent controls (57.4 vs. 52.4), whereas no difference was observed on urethral mobility in the primiparous group (p = 0.25). Urethral sphincter dysfunction and funneling were present in 80% of PI women versus 22.9% in PC women (p < 0.001).ConclusionThe MRI findings revealed that de novo SUI was associated with major LAM injury, vesical neck downward movement as well as urethral sphincter dysfunction. Vesical neck funneling on sagittal images can be treated as a valuable predictor for SUI. The intervention for the PI should focus on the elevation of vesical neck, rehabilitation of LAM as well as recovery of the urethral sphincter muscle.

Dataset Information

Impact of parturition on chemokine homing factor expression in the vaginal distention model of stress urinary incontinence.

Publications

Impact of parturition on chemokine homing factor expression in the vaginal distention model of stress urinary incontinence.

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