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.
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Biaxial Stress Relaxation of Vaginal Tissue in Pubertal Gilts
Abstract Pelvic organ prolapse (POP) is a condition characterized by displacement of the vagina from its normal anatomical position leading to symptoms such as incontinence, physical discomfort, and poor self-image. Conservative treatment has shown limited success and surgical procedures, including the use of mesh, often lead to severe complications. To improve the current treatment methods for prolapse, the viscoelastic properties of vaginal tissue need to be characterized. We determined the biaxial stress relaxation response of vaginal tissue isolated from healthy pubertal gilts. Square specimens (n = 20) with sides aligned along the longitudinal directions (LD) and circumferential direction (CD) of the vagina were biaxially displaced up to 5 N. The specimens were then kept at the displacements corresponding to 5 N for 20 min in both the LD and CD, and the corresponding strains were measured using digital image correlation (DIC). The stresses in the LD and CD were found to decrease by 49.91 ± 5.81% and 46.22 ± 5.54% after 20 min, respectively. The strain in the LD and CD increased slightly from 0.080 ± 0.054 to 0.091 ± 0.064 and 0.050 ± 0.039 to 0.058 ± 0.047, respectively, but these changes were not significant (p > 0.01). By using the Peleg model, the initial decay rate and the asymptotic stress during stress relaxation were found to be significantly higher in the LD than in the CD (p≪0.001), suggesting higher stress relaxation in the LD. These findings may have implications for improving current surgical mesh, mechanical devices, and physical therapy used for prolapse treatment.
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- Award ID(s):
- 1929731
- NSF-PAR ID:
- 10247250
- Date Published:
- Journal Name:
- Journal of Biomechanical Engineering
- Volume:
- 142
- Issue:
- 3
- ISSN:
- 0148-0731
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1115/1.4045707
