Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction

Abstract

Background Although pelvic floor dysfunction (PFD) has a multifactorial etiology, pregnancy and childbirth are considered crucial events predisposing to urinary incontinence as well as pelvic organ prolapse, which are highly prevalent. Rats are the most frequently used animal model and pudendal nerve crush (PNC) and vaginal distension (VD) are often used to mimic vaginal delivery. Objective To document the time course of events after simulated vaginal delivery (SVD) on the urethral sphincter and the vaginal smooth muscle layer. Materials and Methods Virgin female Sprague‐Dawley rats were subjected to SVD (PNC + VD) or sham surgery and evaluated at 7, 14, 21, and 42 days after the injury. Urethral function was determined in vivo by microultrasound during cystometry and vaginal smooth muscle layer was harvested for in vitro pharmacologic investigation by isometric tension recording. Furthermore, vaginal and urethral samples were investigated by immunohistochemistry and real‐time quantitative polymerase chain reaction. Results Microultrasound showed no bursting of the urethral sphincter in the SVD group at 7 days with a functional recovery starting at 14 days, and normal bursting at 21 and 42 days. Vaginal smooth muscle showed higher sensitivity to carbachol at 14 and 21 days after injury; however, at 42 days, its sensitivity decreased when compared with sham. Conclusion SVD induces urethral dysfunction and a shift in vaginal smooth muscle contractile responses to carbachol.

Animal models for pelvic organ prolapse: systematic review

“…Eight studies reported the effects on the vagina [ 53 , 58 , 68 – 73 ] and one on the pelvic floor muscles [ 74 ]. SVD induces structural, active and passive biomechanical changes, which in rats partly heals relatively quickly, but without complete recovery of the muscular layer [ 55 , 68 , 74 ], microvasculature [ 68 ] and biomechanics [ 55 , 68 ]. However, SVD does not lead to POP.…”

“…Significant hypoxia in the epithelial layer and a lower level of hypoxia in the muscularis were observed 1 h after VD [ 71 ]. VD induces a disruption of the fibromuscular layer of the vagina which persists until 4 weeks after delivery [ 68 , 73 ]. On immunochemistry, VD induced an increase in the collagen I/V ratio, but not in the I/III ratio, 4 weeks after delivery and tortuosity of elastic fibers 2 days after VD [ 69 ].…”

“…The downstream pelvic floor dysfunction effects can be measured at different levels, such as urethral and anal sphincter function, but also in the vagina. In several experiments, both strategies (VD and PNC) were combined, though only one focused on vaginal changes [ 68 ]. Active contractility was tested in the vagina at 1, 2, 3 and 6 weeks after VD + PNC.…”

“…Rats are the only species in which effects of delivery were studied by simulating this event (Supplementary Table 3). Eight studies reported the effects on the vagina [53,58,[68][69][70][71][72][73] and one on the pelvic floor muscles [74]. SVD induces structural, active and passive biomechanical changes, which in rats partly heals relatively quickly, but without complete recovery of the muscular layer [55,68,74], microvasculature [68] and biomechanics [55,68].…”

“…No difference [36]; decrease [35,37,34]or increase [30] __ Ambiguous Decrease [30]or increase [34][35][36] Ambiguous No effect [30]; Increase [37]or decrease [ [68,73] Iatrogenic menopause…”