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

Abstract

To investigate the effect of duration of vaginal distention (VD) on the differential expression of stem cell homing and tissue repair cytokines and cytokine receptors in order to identify factors most important for recovery from injury. Twenty 10-week-old virgin Sprague-Dawley rats were divided into 4 groups: 1-hour VD, 4-hour VD, 6-hour VD, and anesthetized shams. Vagina, bladder, urethra and rectum were harvested immediately after VD and Real-Time PCR was used to determine relative expression of cytokines and receptors of interest. Mixed models analysis was used to determine associations between expression level and VD duration. Positive associations between VD duration and level of urethral expression were found for one of the receptors of MCP-3 [CCR1 (p=0.0001)], as well as, for MCP-3 (p=0.025), CCR5 (p=0.032), and HIF1-alpha, (p=0.023). A positive relationship between VD duration and MCP-3 expression was also observed in rectal tissue (p=0.035). Urethral expression of CCR2, another receptor for MCP-3, approached significance (p=0.066). An inverse relationship between VD duration and expression of IL8 was found in the bladder (p=0.0008). No association was demonstrated between VD duration and expression of SDF-1, CXCR4, CCR2, CCR3, and VEGF in any pelvic organs. These data support a relationship between VD duration and subsequent expression of MCP-3 and one of its associated receptors (CCR1) in the urethra immediately following VD. The increase in HIF1-alpha expression in the urethra with prolonged VD suggests a limited role of tissue ischemia in the immediate response of pelvic organs to VD.