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The vagina is a highly inhomogeneous, anisotropic, and viscoelastic organ that undergoes significant deformations in vivo. The mechanical attributes of this organ facilitate important physiological functions during menstruation, intercourse, and birthing. Despite the crucial mechanical role that the vagina plays within the female reproductive system, the deformations that the organ can sustain over time under constant pressure, in both the longitudinal direction (LD) and circumferential direction (CD), have not been fully characterized. This experimental study focuses on quantifying the creep properties of the vagina via ex vivo inflation testing using the rat as an animal model. Toward this end, rat vaginas were subjected to three consecutively increasing constant luminal pressures (28, 55, and 83 kPa) using a custom-built experimental setup and the resulting inhomogeneous deformations were measured using the digital image correlation (DIC) method. The vagina was found to deform significantly more in the CD than the LD at any constant pressure, suggesting that the organ primarily adapts to constant pressures by significantly changing the diameter rather that the length. The change in deformation over time was significantly higher during the first inflation test at a constant pressure of 28 kPa than during the second and third inflation tests at constant pressures of 55 and 83 kPa, respectively. The findings of this study on the mechanical behavior of the vagina could serve to advance our limited knowledge about the physiology and pathophysiology of this important reproductive organ. [ABSTRACT FROM AUTHOR]

Aging is a nonmodifiable risk factor for cardiovascular disease associated with arterial stiffening and endothelial dysfunction. We hypothesized that sex differences exist in vascular aging processes and would be attenuated by global deletion of the G protein-coupled estrogen receptor. Blood pressure was measured by tail-cuff plethysmography, pulse wave velocity (PWV) and echocardiography were assessed with high-resolution ultrasound, and small vessel reactivity was measured using wire myography in adult (25 wk) and middle-aged (57 wk) male and female mice. Adult female mice displayed lower blood pressure and PWV, but this sex difference was absent in middle-aged mice. Aging significantly increased PWV but not blood pressure in both sexes. Adult female carotids were more distensible than males, but this sex difference was lost during aging. Acetylcholine-induced relaxation was greater in female than male mice at both ages, and only males showed aging-induced changes in cardiac hypertrophy and function. GPER deletion removed the sex difference in PWV and ex vivo stiffness in adult mice. The sex difference in blood pressure was absent in KO mice and was associated with endothelial dysfunction in females. These findings indicate that the impact of aging on arterial stiffening and endothelial function is not the same in male and female mice. Moreover, nongenomic estrogen signaling through GPER impacted vascular phenotype differently in male and female mice. Delineating sex differences in vascular changes during healthy aging is an important first step in improving early detection and sex-specific treatments in our aging population. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [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]

Purpose: Racial disparities in preterm birth have been long recognized, but the social and biological mechanisms for these differences are unclear. Our analysis had three goals: (1) to determine the relation between race and other social risk factors and cervical structure; (2) to determine whether social factors mediate the relation between race and cervical structure; and (3) to determine whether racial disparities in preterm birth (PTB) are mediated through changes in cervical structure observed earlier in pregnancy. Materials and methods: Data from the Maternal Fetal Medicine Unit network Preterm Prediction Study were used to examine the relation between race and other social factors and cervical properties throughout pregnancy in 2920 black and white women. Outcomes included cervical length and dilation; cervical score (cervical length–internal dilation); and whether membranes protruded at 22–24 and 26–29 weeks. Race, education, income, insurance type, and marital status were examined as predictors of the outcomes using linear and logistic regression, adjusting for age, BMI, parity, and smoking. Mediation analysis was used to examine whether (a) any social factors explained racial differences in cervical properties, and (b) whether cervical properties mediated racial differences in risk for preterm birth. Results: Shorter cervical length, especially at a subject's first visit, was associated with black race (adjusted beta −1.56 mm, p <.01) and lower income (adjusted beta −1.48, p =.05). External dilation was not associated with social factors, while internal dilation was associated with black race and lower education. Black race and marital status were associated with lower cervical score. There was no evidence of mediation of the racial effect on cervical properties by any social factor. Shorter cervical length, dilation, and score were all associated with preterm birth (p <.01). Mediation analysis indicated that each of these mediated the effect of race, but explained a small proportion of the total effect (15–25%). Conclusions: Race, and, to a lesser extent, other social factors are correlated with adverse cervical properties. This pathway could explain a proportion of the racial disparity in preterm birth. [ABSTRACT FROM AUTHOR]

Our previous work showed that the G protein-coupled estrogen receptor (GPER) is protective in the vasculature and kidneys during angiotensin (Ang) II-dependent hypertension by inhibiting oxidative stress. The goal of the current study was to assess the impact of GPER deletion on sex differences in Ang II-induced hypertension and oxidative stress. Male and female wildtype and GPER knockout mice were implanted with radiotelemetry probes for measurement of baseline blood pressure before infusion of Ang II (700 ng/kg/min) for 2 weeks. Mean arterial pressure was increased to the same extent in all groups, but female wildtype mice were protected from Ang II-induced increases in pulse pressure, aortic wall thickness, and Nox4 mRNA. In vitro studies using vascular smooth muscle cells found that pre-treatment with the GPER agonist G-1 inhibited Ang II-induced ROS and NADP/NADPH. Ang II increased while G-1 decreased Nox4 mRNA and protein. The effects of Ang II were blocked by losartan and Nox4 siRNA, while the effects of G-1 were inhibited by adenylyl cyclase inhibition and mimicked by phosphodiesterase inhibition. We conclude that during conditions of elevated Ang II, GPER via the cAMP pathway suppresses Nox4 transcription to limit ROS production and prevent arterial stiffening. Taken together with our previous work, this study provides insight into how acute estrogen signaling via GPER provides cardiovascular protection during Ang II hypertension and potentially other diseases characterized by increased oxidative stress. [ABSTRACT FROM AUTHOR]

This review discusses sexual dimorphism in arterial stiffening, disease pathology interactions, and the influence of sex on mechanisms and pathways. Arterial stiffness predicts cardiovascular mortality independent of blood pressure. Patients with increased arterial stiffness have a 48% higher risk for developing cardiovascular disease. Like other cardiovascular pathologies, arterial stiffness is sexually dimorphic. Young women have lower stiffness than aged-matched men, but this sex difference reverses during normal aging. Estrogen therapy does not attenuate progressive stiffening in postmenopausal women, indicating that currently prescribed drugs do not confer protection. Although remodeling of large arteries is a protective adaptation to higher wall stress, arterial stiffening increases afterload to the left ventricle and transmits higher pulsatile pressure to smaller arteries and target organs. Moreover, an increase in aortic stiffness may precede or exacerbate hypertension, particularly during aging. Additional studies are needed to elucidate the mechanisms by which females are protected from arterial stiffness to provide insight into its mechanisms and, ultimately, therapeutic targets for treating this pathology. [ABSTRACT FROM AUTHOR]

Purpose: Racial disparities in preterm birth have been long recognized, but the social and biological mechanisms for these differences are unclear. Our analysis had three goals: (1) to determine the relation between race and other social risk factors and cervical structure; (2) to determine whether social factors mediate the relation between race and cervical structure; and (3) to determine whether racial disparities in preterm birth (PTB) are mediated through changes in cervical structure observed earlier in pregnancy. Materials and methods: Data from the Maternal Fetal Medicine Unit network Preterm Prediction Study were used to examine the relation between race and other social factors and cervical properties throughout pregnancy in 2920 black and white women. Outcomes included cervical length and dilation; cervical score (cervical length-internal dilation); and whether membranes protruded at 22-24 and 26-29 weeks. Race, education, income, insurance type, and marital status were examined as predictors of the outcomes using linear and logistic regression, adjusting for age, BMI, parity, and smoking. Mediation analysis was used to examine whether (a) any social factors explained racial differences in cervical properties, and (b) whether cervical properties mediated racial differences in risk for preterm birth. Results: Shorter cervical length, especially at a subject's first visit, was associated with black race (adjusted beta -1.56 mm, p < .01) and lower income (adjusted beta -1.48, p =.05). External dilation was not associated with social factors, while internal dilation was associated with black race and lower education. Black race and marital status were associated with lower cervical score. There was no evidence of mediation of the racial effect on cervical properties by any social factor. Shorter cervical length, dilation, and score were all associated with preterm birth (p < .01). Mediation analysis indicated that each of these mediated the effect of race, but explained a small proportion of the total effect (15-25%). Conclusions: Race, and, to a lesser extent, other social factors are correlated with adverse cervical properties. This pathway could explain a proportion of the racial disparity in preterm birth. [ABSTRACT FROM AUTHOR]

The mRen2 female rat is an estrogen- and salt-sensitive model of hypertension that reflects the higher pressure and salt sensitivity associated with menopause. We previously showed that the G protein-coupled estrogen receptor (GPER) mediates estrogenic effects in this model. The current study hypothesized that GPER protects against vascular injury during salt loading. Intact mRen2 female rats were fed a normal (NS; 0.5% Na±) or high-salt diet (HS; 4% Na±) for 10 wk, which significantly increased systolic blood pressure (149 ± 5 vs. 224 ± 8 mmHg; P ± 0.001). Treatment with the selective GPER agonist G-1 for 2 wk did not alter salt-sensitive hypertension (216 ± 4 mmHg; P ± 0.05) or ex vivo vascular responses to angiotensin II or phenylephrine (P ± 0.05). However, G-1 significantly attenuated salt-induced aortic remodeling assessed by media-to-lumen ratio (NS: 0.43; HS±veh: 0.89; HS±G-1: 0.61; P ± 0.05). Aortic thickening was not accompanied by changes in collagen, elastin, or medial proliferation. However, HS induced increases in medial layer glycosaminoglycans (0.07 vs. 0.42 mm2; P ± 0.001) and lipid peroxidation (0.11 vs. 0.51 mm2; P ± 0.01), both of which were reduced by G-1 (0.20 mm2 and 0.23 mm2; both P ± 0.05). We conclude that GPER's beneficial actions in the aorta of salt-loaded mRen2 females occur independently of changes in blood pressure and vasoreactivity. GPER-induced attenuation of aortic remodeling was associated with a reduction in oxidative stress and decreased accumulation of glycosaminoglycans. Endogenous activation of GPER may protect females from salt- and pressure-induced vascular damage. [ABSTRACT FROM AUTHOR]

Crimp morphology is believed to be related to tendon mechanical behavior. While crimp has been extensively studied at slack or nondescript load conditions in tendon, few studies have examined crimp at specific, quantifiable loading conditions. Additionally, the effect of the number of cycles of preconditioning on collagen fiber crimp behavior has not been examined. Further, the dependence of collagen fiber crimp behavior on location and developmental age has not been examined in the supraspinatus tendon. Local collagen fiber crimp frequency is quantified throughout tensile mechanical testing using a flash freezing method immediately following the designated loading protocol. Samples are analyzed quantitatively using custom software and semi-quantitatively using a previously established method to validate the quantitative software. Local collagen fiber crimp frequency values are compared throughout the mechanical test to determine where collagen fiber frequency changed. Additionally, the effect of the number of preconditioning cycles is examined compared to the preload and toe-region frequencies to determine if increasing the number of preconditioning cycles affects crimp behavior. Changes in crimp frequency with age and location are also examined. Decreases in collagen fiber crimp frequency were found at the toe-region at all ages. Significant differences in collagen fiber crimp frequency were found between the preload and after preconditioning points at 28 days. No changes in collagen fiber crimp frequency were found between locations or between 10 and 28 days old. Local collagen fiber crimp frequency throughout mechanical testing in a postnatal developmental mouse SST model was measured. Results confirmed that the uncrimping of collagen fibers occurs primarily in the toe-region and may contribute to the tendon's nonlinear behavior. Additionally, results identified changes in collagen fiber crimp frequency with an increasing number of preconditioning cycles at 28 days, which may have implications on the measurement of mechanical properties and identifying a proper reference configuration. [ABSTRACT FROM AUTHOR]

Repeatedly and consistently measuring the mechanical properties of tendon is important but presents a challenge. Preconditioning can provide tendons with a consistent loading history to make comparisons between groups from mechanical testing experiments. However, the specific mechanisms occurring during preconditioning are unknown. Previous studies have suggested that microstructural changes, such as collagen fiber re-alignment, may be a result of preconditioning. Local collagen fiber re-alignment is quantified throughout tensile mechanical testing using a testing system integrated with a polarized light setup, consisting of a backlight, 90 deg-offset rotating polarizer sheets on each side of the test sample, and a digital camera, in a rat supraspinatus tendon model, and corresponding mechanical properties are measured. Local circular variance values are compared throughout the mechanical test to determine if and where collagen fiber re-alignment occurred. The inhomogeneity of the tendon is examined by comparing local circular variance values, optical moduli and optical transition strain values. Although the largest amount of" collagen fiber re-alignment was found during preconditioning, significant re-alignment was also demonstrated in the toe and linear regions of the mechanical test. No significant changes in re-alignment were seen during stress relaxation. The insertion site of the supraspinatus tendon demonstrated a lower linear modulus and a more disorganized collagen fiber distribution throughout all mechanical testing points compared to the tendon midsubstance. This study identified a correlation between collagen fiber re-alignment and preconditioning and suggests that collagen fiber re-alignment may be a potential mechanism of preconditioning and merits further investigation. In particular, the conditions necessary for collagen fibers to re-orient away from the direction of loading and the dependency of collagen reorganization on its initial distribution must be examined. [ABSTRACT FROM AUTHOR]