Cytokine Expression After Vaginal Distention of Different Durations in Virgin Sprague-Dawley Rats

Wood, Hadley M.; Kuang, Mei; Woo, Lynn L.; Hijaz, Adonis; Butler, Robert S.; Penn, Marc S.; Rackley, Raymond R.; Damaser, Margot S.

doi:10.1016/j.juro.2008.03.182

Cited by 39 publications

(53 citation statements)

References 20 publications

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“…This is consistent with previous work showing marked edema after 4 h of VD associated with thinning of the UVS and interstitial swelling between striated muscle fibers (28). In addition, we previously showed that the urethra is the only organ demon- strating a significant increase in hypoxia-inducible factor-1␣ after VD (52), indicative of more significant hypoxia in this organ than other pelvic organs. Therefore, the edema could have occurred as a consequence of tissue inflammation secondary to hypoxia (54).…”

Section: Discussionsupporting

confidence: 93%

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Vulnerability of continence structures to injury by simulated childbirth

Phull

Pan

Butler

et al. 2011

American Journal of Physiology-Renal Physiology

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The goal of this study was to examine acute morphological changes, edema, muscle damage, inflammation, and hypoxia in urethral and vaginal tissues with increasing duration of vaginal distension (VD) in a rat model. Twenty-nine virgin Sprague-Dawley rats underwent VD under anesthesia with the use of a modified Foley catheter inserted into the vagina and filled with saline for 0, 1, 4, or 6 h. Control animals were anesthetized for 4 h without catheter placement. Urogenital organs were harvested after intracardiac perfusion of fixative. Tissues were embedded, sectioned, and stained with Masson's trichrome or hematoxylin and eosin stains. Regions of hypoxia were measured by hypoxyprobe-1 immunohistochemistry. Within 1 h of VD, the urethra became vertically elongated and displaced anteriorly. Edema was most prominent in the external urethral sphincter (EUS) and urethral/vaginal septum within 4 h of VD, while muscle disruption and fragmentation of the EUS occurred after 6 h. Inflammatory damage was characterized by the presence of polymorphonuclear leukocytes in vessels and tissues after 4 h of VD, with the greatest degree of infiltration occurring in the EUS. Hypoxia localized mostly to the vaginal lamina propria, urethral smooth muscle, and EUS within 4 h of VD. Increasing duration of VD caused progressively greater tissue edema, muscle damage, and morphological changes in the urethra and vagina. The EUS underwent the greatest insult, demonstrating its vulnerability to childbirth injury.

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Section: Discussionsupporting

confidence: 93%

“…The most commonly utilized model consists of VD with a Foley catheter balloon (8,28). Longer-duration distension has been shown to have more severe outcomes with a longer recovery time (37,52). In addition, hypoxia and reperfusion have been shown to be likely mechanisms for the injury to continence structures during VD (12,46,54).…”

Section: Discussionmentioning

confidence: 99%

Vulnerability of continence structures to injury by simulated childbirth

Phull

Pan

Butler

et al. 2011

American Journal of Physiology-Renal Physiology

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“…The lack of differences in rectal MCP-3 expression after VD injury in our study is consistent with the findings of Woo et al, 22,23 but is in contrast to the findings of Wood et al 13 who observed a 21-fold increase in relative MCP-3 expression in the rectum immediately after VD injury. It should be noted, however, that in the Wood study this difference was only seen after 4 hours of sustained VD injury, as there was no relative difference in MCP-3 expression after 1 hour of VD as compared to controls.…”

Section: Commentsupporting

confidence: 91%

“…13 MCP-3 is a mesenchymal stem cell (MSC) homing cytokine, which plays a key role in post-ischemia recovery. 14 Moreover, we have demonstrated selective homing of intravenously infused MSCs to the urethra, following VD.…”

Section: Introductionmentioning

confidence: 99%

Expression of Monocyte Chemotactic Protein 3 Following Simulated Birth Trauma in a Murine Model of Obesity

Vricella

Tao

Altuntas

et al. 2010

Urology

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Objective To determine the effect of obesity on simulated birth trauma in leptin-deficient obese mice as measured by relative MCP-3 expression. Materials and Methods A total of 25 wild-type and 25 obese C57BL/6 virgin female mice underwent 1 hour of vaginal distension (VD), sham VD or anesthesia without VD. Pelvic organ tissues were then harvested either immediately or 24-hours post VD and subsequent real-time PCR analysis was performed. Results Urethral MCP-3 levels in wild-type mice were elevated from baseline at 0-hours with a return to baseline at 24-hours in both VD and sham VD groups. In obese mice, there was a 6-fold elevation in MCP-3 levels at 0-hours after sham VD versus control (P < 0.05), which then returned to baseline levels at 24-hours. After undergoing VD, MCP-3 levels increased to 6-fold baseline values (P = 0.002) at 0-hours, with continued elevation in MCP-3 levels to 15 times control levels (P = 0.0003) at 24-hours. Conclusions MCP-3 is significantly over expressed in the urethral tissues of both wild-type and obese mice immediately after any urethral manipulation. At 24-hours, the MCP-3 expression patterns become divergent between VD and sham VD in obese mice. With a greater degree of trauma, MCP-3 continued to rise at 24-hours, suggesting that the underlying obesity resulted in alterations in response to tissue injury paralleling the degree of injury. Such associations warrant further investigation into the role of MCP-3 as a chemokine for stem cell migration with implications for subsequent tissue repair mechanisms after birth trauma.

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“…These time points were selected based on the timecourse of cytokine expression in previous studies. 7,9,22,25,26 Loxl1 KO mouse gestation duration is approximately 21 days, so, as a feasible time point for studying the effects of pregnancy in the absence of delivery as a control for delivered mice, tissues were harvested on the 20 th day of gestation, prior to parturition for the pregnant group (Figure 1A). Sixty-four additional age-matched virgin Loxl1 KO female mice were utilized as sham cesarean injury controls or unmanipulated virgin controls (Figure 1A).…”

Section: Methodsmentioning

confidence: 99%

Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse

Couri

Borazjani

Balog

et al. 2017

Female Pelvic Med Reconstr Surg

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Objectives The aim of this study was to determine the effect of pregnancy and delivery mode on cytokine expression in the pelvic organs and serum of lysyl oxidase like-1 knockout (Loxl1 KO) mice, which develop pelvic organ prolapse (POP) after delivery. Methods Bladder, urethra, vagina, rectum and blood were harvested from female Loxl1 KO mice during pregnancy, after vaginal or cesarean delivery, and from sham cesarean and unmanipulated controls. Pelvic organs and blood were also harvested from pregnant and vaginally delivered wild-type (WT) mice and from unmanipulated female virgin WT controls. Specimens were assessed using qRT-PCR and/or ELISA. Results Both Cxcl12 and Ccl7 mRNA were significantly upregulated in the vagina, urethra, bladder, and rectum of pregnant Loxl1 KO mice compared to pregnant WT mice, suggesting systemic dysregulation of both of these cytokines in Loxl1 KO mice as a response to pregnancy. The differences in cytokine expression between Loxl1 KO and WT mice in pregnancy persisted after vaginal delivery. Ccl7 gene expression increases faster and to a greater extent in Loxl1 KO mice, translating to longer lasting increases in CCL7 in serum of Loxl1 KO mice after vaginal delivery, compared to pregnant mice. Conclusions Loxl1 KO mice have an increased cytokine response to pregnancy, perhaps because they are less able to reform and re-crosslink stretched elastin to accommodate pups and this resultant tissue stretches during pregnancy. Upregulation of CCL7 after delivery could provide an indicator of level of childbirth injury, to which the urethra and vagina appear to be particularly vulnerable.

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Cytokine Expression After Vaginal Distention of Different Durations in Virgin Sprague-Dawley Rats

Cited by 39 publications

References 20 publications

Vulnerability of continence structures to injury by simulated childbirth

Vulnerability of continence structures to injury by simulated childbirth

Expression of Monocyte Chemotactic Protein 3 Following Simulated Birth Trauma in a Murine Model of Obesity

Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse

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