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Advanced maternal age during pregnancy is associated with increased risk of vaginal tearing during delivery and maladaptive postpartum healing. Although the underlying mechanisms of age-related vaginal injuries are not fully elucidated, changes in vaginal microstructure may contribute. Smooth muscle cells promote the contractile nature of the vagina and contribute to pelvic floor stability. While menopause is associated with decreased vaginal smooth muscle content, whether contractile changes occur before the onset of menopause remains unknown. Therefore, the first objective of this study was to quantify the active mechanical behavior of the murine vagina with age. Further, aging is associated with decreased vaginal elastin content. As such, the second objective was to determine if elastic fiber disruption alters vaginal contractility. Vaginal samples from mice aged 2–14 months were used in maximum contractility experiments and biaxial extension-inflation protocols. To evaluate the role of elastic fibers with age, half of the vaginal samples were randomly allocated to enzymatic elastic fiber disruption. Contractile potential decreased and vaginal material stiffness increased with age. These age-related changes in smooth muscle function may be due, in part, to changes in microstructural composition or contractile gene expression. Furthermore, elastic fiber disruption had a diminished effect on smooth muscle contractility in older mice. This suggests a decreased functional role of elastic fibers with age. Quantifying the age-dependent mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties provides a first step towards better understanding how age-related changes in vaginal structure may contribute to tissue integrity and healing. Advanced maternal age at the time of pregnancy is linked to increased risks of vaginal tearing during delivery, postpartum hemorrhaging, and the development of pelvic floor disorders. While the underlying causes of increased vaginal injuries with age and associated pathologies remain unclear, changes in vaginal microstructure, such as elastic fibers and smooth muscle cells, may contribute. Menopause is associated with fragmented elastic fibers and decreased smooth muscle content; however, how reproductive aging affects changes in the vaginal composition and the mechanical properties remains unknown. Quantifying the mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties with age will advance understanding of the potential structural causes of age-related changes to tissue integrity and healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Mammalian pregnancy requires gradual yet extreme remodeling of the reproductive organs to support the growth of the embryos and their birth. After delivery, the reproductive organs return to their non-pregnant state. As pregnancy has traditionally been understudied, there are many unknowns pertaining to the mechanisms behind this remarkable remodeling and repair process which, when not successful, can lead to pregnancy-related complications such as maternal trauma, pre-term birth, and pelvic floor disorders. This study presents the first longitudinal imaging data that focuses on revealing anatomical alterations of the vagina, cervix, and uterine horns during pregnancy and postpartum using the mouse model. By utilizing advanced magnetic resonance imaging (MRI) technology, T1-weighted and T2-weighted images of the reproductive organs of three mice in their in vivo environment were collected at five time points: non-pregnant, mid-pregnant (gestation day: 9–10), late pregnant (gestation day: 16–17), postpartum (24–72 h after delivery) and three weeks postpartum. Measurements of the vagina, cervix, and uterine horns were taken by analyzing MRI segmentations of these organs. The cross-sectional diameter, length, and volume of the vagina increased in late pregnancy and then returned to non-pregnant values three weeks after delivery. The cross-sectional diameter of the cervix decreased at mid-pregnancy before increasing in late pregnancy. The volume of the cervix peaked at late pregnancy before shortening by 24–72 h postpartum. As expected, the uterus increased in cross-sectional diameter, length, and volume during pregnancy. The uterine horns decreased in size postpartum, ultimately returning to their average non-pregnant size three weeks postpartum. The newly developed methods for acquiring longitudinal in vivo MRI scans of the murine reproductive system can be extended to future studies that evaluate functional and morphological alterations of this system due to pathologies, interventions, and treatments. [ABSTRACT FROM AUTHOR]

Background: Pelvic organ prolapse (POP) affects a significant portion of the female population, impacting quality of life and often requiring intervention. The exact cause of prolapse is unknown. Methods: We review some of the current research that focuses on defining the elements involved in POP, with a focus on in vitro testing. Results: Treatment for POP, ranging fromphysical therapy or pessary use to more invasive surgery, has varying success rates. This variation is, in part, because the pathophysiology of pelvic floor support--and thus dysfunction--is incompletely understood, particularly regarding the structural components and biomechanical properties of tissue. However, researchers are working to identify and quantify the structural and functional dysfunction that may lead to the development of this condition. Conclusion: Given the limited understanding of prolapse development, more research is needed to quantify the microstructure of the pelvic organs and pelvic support structures, with and without prolapse. Identifying biomechanical properties in multiaxial configurations will improve our understanding of pelvic tissue support, as well as our ability to establish predictive models and improve clinical treatment strategies. [ABSTRACT FROM AUTHOR]

Uterosacral ligaments (USLs) provide structural support to the female pelvic floor, and a loss of USL structural integrity or biomechanical function may induce pelvic organ prolapse (POP). Alterations in extracellular matrix composition and organization dictate USL mechanical function. Changes in USL microstructure and corresponding mechanical properties, however, are not fully understood, nor is it understood how microstructure and mechanics change with onset and progression of POP. This is due, in part, as USL properties are primarily characterized along a single direction (uniaxial test), whereas the USL is loaded in multiple directions simultaneously within the body. Biaxial testing permits the acquisition of biomechanical data from two axes simultaneously, and thus simulates a more physiologic assessment compared to the traditional uniaxial testing. Therefore, the objective of this study was to quantify the biaxial biomechanical properties and histological composition of the USL in post-menopausal women with and without POP at various stages. Potential correlations between tissue microstructural composition and mechanical function were also examined. Tangential modulus was lower and peak stretch higher in POP III/IV compared to non-POP and POP I/II in the main in vivo loading direction; however, no significant differences in mechanical properties were observed in the perpendicular loading direction. Collagen content positively correlated to tangential modulus in the main in vivo loading direction (r = 0.5, p = 0.02) and negatively correlated with the peak stretch in both the main in vivo (r = −0.5, p = 0.02) and perpendicular loading directions (r = −0.3, p = 0.05). However, no statistically significant differences in USL composition were observed, which may be due to the small sample size and high variability of small sections of human tissues. These results provide first step towards understanding what microstructural and mechanical changes may occur in the USL with POP onset and progression. Such information may provide important future insights into the development of new surgical reconstruction techniques and graft materials for POP treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Mounting evidence suggests that cells within soft tissues seek to maintain a preferred biomechanical state. Residual stress is defined as the stress that remains in a tissue when all external loads are removed and contributes to tissue mechanohomeostasis by decreasing the transmural gradient of wall stress. Current computational models of pelvic floor mechanics, however, often do not consider residual stress. Residual strain, a result of residual stress can be quantitatively measured through opening angle experiments. Therefore, the objective of this study is to quantify the regional variations in opening angles along the murine female reproductive system at estrus and diestrus, to quantify residual strain in the maintenance state of sexually mature females. Further, evidence suggests that hydrophilic glycosaminoglycan/proteoglycans are integral to cervical remodeling. Thus, variations in opening angles following hypo-osmotic loading are evaluated. Opening angle experiments were performed along the murine reproductive system in estrus (n = 8) and diestrus (n = 8) and placed in hypo-osmotic solution. Measurements of thickness and volume were also obtained for each group. Differences (p < 0.05) in opening angle were observed with respect to region and loading, however, differences with respect to estrous stage were not significant. Thickness values were significant (p < 0.05) with respect to region only. The effects of both estrous cycle and region resulted in significant differences (p < 0.05) in observed volume. The observed regional differences indicate variation in the stress-free state among the reproductive system which may have implications for future computational models to advance women's reproductive health. [ABSTRACT FROM AUTHOR]