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1. Role of fibulin-5 insufficiency and prolapse progression on murine vaginal biomechanical function

   https://doi.org/10.1038/s41598-021-00351-1  

   Clark-Patterson, Gabrielle L.; Roy, Sambit; Desrosiers, Laurephile; Knoepp, Leise R.; Sen, Aritro; Miller, Kristin S. (December 2021, Scientific Reports)

   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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2. The Effect of Menopause on Vaginal Tissue Mechanics: A Brief Review

   https://doi.org/10.1115/1.4063101  

   Gimenez, Clara; Alperin, Marianna; De_Vita, Raffaella (June 2024, Journal of Biomechanical Engineering)

   Abstract Often called “the change of life,” menopause affects every part of a woman's body. As the sex hormones decrease, the reproductive organs experience the most remarkable changes, with the vagina becoming thinner, drier, and less elastic. Despite the important implications of these changes in genitourinary conditions, there are only a few experimental studies that focus on quantifying the effect of menopause on the mechanical properties of the vagina. These studies are mostly conducted using uniaxial tests on strips of vaginal tissues isolated from rats, rabbits, and sheep and, in only a few cases, from humans. The purpose of this article is to present a systematic review of experimental protocols, methods, and results that are currently published on how menopause alters the mechanical behavior of the vagina. This review will enable new investigators in the biomechanics field to identify important gaps and frame research questions that inform the design of new treatment options for menopausal symptoms. 

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3. Contractile Properties of Vaginal Tissue

   https://doi.org/10.1115/1.4046712  

   Huntington, Alyssa; Donaldson, Kandace; De Vita, Raffaella (August 2020, Journal of Biomechanical Engineering)

   null (Ed.)

   Abstract The vagina is an important organ of the female reproductive system that has been largely understudied in the field of biomechanics. In recent years, some research has been conducted to evaluate the mechanical properties of the vagina, but much has focused on characterizing the passive mechanical properties. Because vaginal contractions play a central role in sexual function, childbirth, and development and treatment of pelvic floor disorders, the active mechanical properties of the vagina must be also quantified. This review surveys and summarizes published experimental studies on the active properties of the vagina including the differences in such properties determined by anatomic regions and orientations, neural pathways, life events such as pregnancy and menopause, pelvic floor disorders such as prolapse, and surgical mesh treatment. Conflicting experimental findings are presented, illustrating the need for further research on the active properties of the vagina. However, consensus currently exists regarding the negative impact of surgical mesh on vaginal contractility. This review also identifies knowledge gaps and future research opportunities, thus proving a firm foundation for novice and experienced researchers in this emerging area of biomechanics and encouraging more activity on women's sexual and reproductive health research. 

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4. Elastin haploinsufficiency in mice has divergent effects on arterial remodeling with aging depending on sex

   https://doi.org/10.1152/ajpheart.00517.2020  

   Hawes, Jie Z.; Cocciolone, Austin J.; Cui, Amy H.; Griffin, Diana B.; Staiculescu, Marius Catalin; Mecham, Robert P.; Wagenseil, Jessica E. (December 2020, American Journal of Physiology-Heart and Circulatory Physiology)

   null (Ed.)

   Elastin is a primary structural protein in the arterial wall that contributes to vascular mechanical properties and degrades with aging. Aging is associated with arterial stiffening and an increase in blood pressure. There is evidence that arterial aging follows different timelines with sex. Our objective was to investigate how elastin content affects arterial remodeling in male and female mice with aging. We used male and female wild-type ( Eln +/+ ) and elastin heterozygous ( Eln +/− ) mice at 6, 12, and 24 mo of age and measured their blood pressure and arterial morphology, wall structure, protein content, circumferential stress, stretch ratio, and stiffness. Two arteries were used with varying contents of elastin: the left common carotid and ascending aorta. We show that Eln +/− arteries start at a different homeostatic set point for circumferential wall stress, stretch, and material stiffness but show similar increases with aging to Eln +/+ mice. With aging, structural stiffness is greatly increased, while material stiffness and circumferential stress are only slightly increased, highlighting the importance of maintaining these homeostatic values. Circumferential stretch shows the smallest change with age and may be important for controlling cellular phenotype. Independent sex differences are mostly associated with males being larger than females; however, many of the measured factors show age × sex and/or genotype × sex interactions, indicating that males and females follow different cardiovascular remodeling timelines with aging and are differentially affected by reduced elastin content. NEW & NOTEWORTHY A comprehensive study on arterial mechanical behavior as a function of elastin content, aging, and sex in mice. Elastin haploinsufficient arteries start at a different homeostatic set point for mechanical parameters such as circumferential stress, stretch, and material stiffness. Structural stiffness of the arterial wall greatly increases with aging, as expected, but there are interactions between sex and aging for most of the mechanical parameters that are important to consider in future work. 

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5. Investigation of Murine Vaginal Creep Response to Altered Mechanical Loads

   https://doi.org/10.1115/1.4052365  

   Clark-Patterson, Gabrielle L.; McGuire, Jeffrey A.; Desrosiers, Laurephile; Knoepp, Leise R.; De Vita, Raffaella; Miller, Kristin S. (December 2021, Journal of Biomechanical Engineering)

   Abstract The vagina is a viscoelastic fibromuscular organ that provides support to the pelvic organs. The viscoelastic properties of the vagina are understudied but may be critical for pelvic stability. Most studies evaluate vaginal viscoelasticity under a single uniaxial load; however, the vagina is subjected to dynamic multiaxial loading in the body. It is unknown how varied multiaxial loading conditions affect vaginal viscoelastic behavior and which microstructural processes dictate the viscoelastic response. Therefore, the objective was to develop methods using extension-inflation protocols to quantify vaginal viscoelastic creep under various circumferential and axial loads. Then, the protocol was applied to quantify vaginal creep and collagen microstructure in the fibulin-5 wildtype and haploinsufficient vaginas. To evaluate pressure-dependent creep, the fibulin-5 wildtype and haploinsufficient vaginas (n = 7/genotype) were subjected to various constant pressures at the physiologic length for 100 s. For axial length-dependent creep, the vaginas (n = 7/genotype) were extended to various fixed axial lengths then subjected to the mean in vivo pressure for 100 s. Second-harmonic generation imaging was performed to quantify collagen fiber organization and undulation (n = 3/genotype). Increased pressure significantly increased creep strain in the wildtype, but not the haploinsufficient vagina. The axial length did not significantly affect the creep rate or strain in both genotypes. Collagen undulation varied through the depth of the subepithelium but not between genotypes. These findings suggest that the creep response to loading may vary with biological processes and pathologies, therefore, evaluating vaginal creep under various circumferential loads may be important to understand vaginal function. 

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