Background Vaginal delivery and aging are key risk factors for pelvic floor muscle dysfunction, which is a critical component of pelvic floor disorders. However, alterations in the PFM intrinsic structure due to childbirth and aging that lead to muscle dysfunction remain elusive. Objectives To determine the impact of vaginal deliveries and aging on human cadaveric PFM architecture, the strongest predictor of active muscle function. Study Design Coccygeus, iliococcygeus and pubovisceralis were obtained from younger, ≤ 51 years, vaginally nulliparous (N=5) and vaginally parous (N=6), and older, >51 years, vaginally nulliparous (N=6) and vaginally parous (N=6) donors without history of PFDs. Architectural parameters, predictive of muscle’s excursion and force-generating capacity, were determined using validated methods. Intramuscular collagen content was quantified by hydroxyproline assay. Main effects of parity and aging and the interactions were determined using two-way ANOVA, with Tukey’s post-hoc testing with significance level of 0.05. Results The mean age of younger and older donors differed by ~40 years (P=0.001), but was similar between nulliparous and parous donors within each age group (P>0.9). Median parity was 2 (range 1–3) in younger and older vaginally parous groups, P=0.7. The main impact of parity was increased fiber length in the more proximal coccygeus (P=0.03), and iliococcygeus (P=0.04). Aging changes manifested as decreased physiological cross sectional area across all pelvic floor muscles, P<0.05, which substantially exceeded the age-related decline in muscle mass. Physiological cross sectional area was lower in younger vaginally parous, compared to younger vaginally nulliparous pelvic floor muscles, however the differences did not reach statistical significance. Pelvic floor muscles’ collagen content was not altered by parity, but increased dramatically with aging, P<0.05. Conclusions Increased fiber length in more proximal pelvic floor muscles likely represents an adaptive response to the chronically increased load placed on these muscles by the displaced apical structures, presumably as a consequence of vaginal delivery. In younger specimens, a consistent trend towards decrease in force generating capacity of all pelvic floor muscles in parous group suggests a potential mechanism for clinically identified pelvic floor muscle weakness in vaginally parous women. The substantial decrease in predicted muscle force production and fibrosis with aging represent likely mechanisms for the pelvic floor muscle dysfunction in older women.

Study Design-Cadaveric analysis of human abdominal muscle architecture.Objective-To quantify the architectural properties of rectus abdominis (RA), external oblique (EO), internal oblique (IO) and transverse abdominis (TrA), and model mechanical function in light of these new data.Summary of Background Data-Knowledge of muscle architecture provides the structural basis for predicting muscle function. Abdominal muscles greatly affect spine loading, stability, injury prevention and rehabilitation; however, their architectural properties are unknown.Methods-Abdominal muscles from eleven elderly human cadavers were removed intact, separated into regions and micro-dissected for quantification of physiological cross-sectional area (PCSA), fascicle length and sarcomere length. From these data, sarcomere operating length ranges were calculated.Results-IO had the largest PCSA and RA the smallest, and would thus generate the largest and smallest isometric forces, respectively. RA had the longest fascicle length, followed by EO, and would thus be capable of generating force over the widest range of lengths. Measured sarcomere lengths, in the post-mortem neutral spine posture, were significantly longer in RA and EO (3.29±0.07 and 3.18±0.11 μm) compared to IO and TrA (2.61±0.06 and 2.58±0.05 μm) (p < 0.0001). Biomechanical modeling predicted that RA, EO and TrA act at optimal force-generating length in the mid-range of lumbar spine flexion, where IO can generate approximately 90% of its maximum force.Conclusions-These data provide clinically relevant insights into the ability of the abdominal wall muscles to generate force and change length throughout the lumbar spine range of motion. NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976 This will impact the understanding of potential postures in which the force-generating and spine stabilizing ability of these muscles become compromised, which can guide exercise/rehabilitation development and prescription. Future work should explore the mechanical interactions among these muscles and their relationship to spine health and function.

SUMMARY The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy – titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to ‘tune’ the protein's mechanotransduction capability.

Pelvic floor disorders, which include pelvic organ prolapse, and urinary and fecal incontinence, affect millions of women globally and represent a major public health concern. Pelvic floor muscle (PFM) dysfunction has been identified as one of the leading risk factors for the development of these morbid conditions. Even though childbirth, specifically vaginal delivery, has been long recognized as the most important potentially modifiable risk factor for PFM injury, the precise mechanisms of PFM dysfunction following childbirth remain elusive. In this study we demonstrate that PFMs undergo atrophy and severe fibrosis in parous women with symptomatic pelvic organ prolapse compared to age-matched nulliparous cadaveric donors without history of pelvic floor disorders. These pathological alterations are recapitulated in the pre-clinical rat model of simulated birth injury. The transcriptional signature of PFMs post-injury demonstrates a sustained inflammatory response, impairment in muscle anabolism, and persistent expression of extracellular matrix (ECM) remodeling genes. Next, we evaluated the administration of acellular injectable skeletal muscle extracellular matrix hydrogel for the prevention and mitigation of these pathological alterations. Treatment of PFMs with the biomaterial either at the time of birth injury or 4 weeks post-injury reduced muscle atrophy and mitigated fibrotic degeneration. By evaluating gene expression, we demonstrate that these changes are mainly driven by the hydrogel-induced modulation of the immune response and intramuscular fibrosis, as well as enhancement of the endogenous myogenesis. This work furthers our understanding of PFM birth injury and demonstrates proof-of-concept for a new pragmatic pro-regenerative biomaterial approach for treating injured PFMs.