Abstract
The vagina plays a critical role in supporting the pelvic organs and loss of support leads to pelvic organ prolapse. It is unknown what microstructural changes influence prolapse progression nor how decreased elastic fibers contributes to vaginal remodeling and smooth muscle contractility. The objective for this study was to evaluate the effect of fibulin-5 haploinsufficiency, and deficiency with progressive prolapse on the biaxial contractile and biomechanical function of the murine vagina. Vaginas from wildtype (n = 13), haploinsufficient (n = 13), and deficient mice with grade 1 (n = 9) and grade 2 or 3 (n = 9) prolapse were explanted for biaxial contractile and biomechanical testing. Multiaxial histology (n = 3/group) evaluated elastic and collagen fiber microstructure. Western blotting quantified protein expression (n = 6/group). A one-way ANOVA or Kruskal–Wallis test evaluated statistical significance. Pearson’s or Spearman’s test determined correlations with prolapse grade. Axial contractility decreased with fibulin-5 deficiency and POP (p < 0.001), negatively correlated with prolapse grade (ρ = − 0.80; p < 0.001), and positively correlated with muscularis elastin area fraction (ρ = − 0.78; p = 0.004). Circumferential (ρ = 0.71; p < 0.001) and axial (ρ = 0.69; p < 0.001) vaginal wall stresses positively correlated with prolapse grade. These findings demonstrated that fibulin-5 deficiency and prolapse progression decreased vaginal contractility and increased vaginal wall stress. Future work is needed to better understand the processes that contribute to prolapse progression in order to guide diagnostic, preventative, and treatment strategies.
Highlights
The vagina plays a critical role in supporting the pelvic organs and loss of support leads to pelvic organ prolapse
Elastic fibers consist of various structural components that are important for the assembly into a mature and functional fiber
Women with POP have stiffer vaginal tissue, which correlates with POP severity, compared to non-POP controls[23,24,25,26,27]. It is not known what microstructural changes influence POP progression, nor how decreased elastic fibers contribute to vaginal remodeling and smooth muscle cell (SMC) contractility
Summary
The vagina plays a critical role in supporting the pelvic organs and loss of support leads to pelvic organ prolapse. Women with POP have stiffer vaginal tissue, which correlates with POP severity, compared to non-POP controls[23,24,25,26,27] It is not known what microstructural changes influence POP progression, nor how decreased elastic fibers contribute to vaginal remodeling and SMC contractility. By 6 months of age 92% of fibulin-5 deficient mice develop POP where the vagina and cervix are descended, stretched, and herniated through the vaginal canal[10] This animal model can serve as a useful tool to evaluate vaginal connective tissue remodeling associated with POP progression, and to determine how changes in elastic fiber content with altered fibulin-5 expression (i.e., deficiency and haploinsufficiency) affects vaginal function. Extension-inflation protocols, which have the ability to maintain vaginal geometry and native SMC-matrix interactions, are useful biaxial biomechanical testing m ethods[31,32,33,34]
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