Architectural assessment of rhesus macaque pelvic floor muscles: comparison for use as a human model

Abstract

Introduction and hypothesis Animal models are essential to further our understanding of the independent and combined function of human pelvic floor muscles (PFMs), as direct studies in women are limited. To assure suitability of the rhesus macaque (RM), we compared RM and human PFM architecture, the strongest predictor of muscle function. We hypothesized that relative to other models, RM best resembles human PFM. Methods Major architectural parameters of cadaveric human coccygeus, iliococcygeus, and pubovisceralis (pubococcygeus + puborectalis) and corresponding RM coccygeus, iliocaudalis, and pubovisceralis (pubovaginalis + pubocaudalis) were compared using 1- and 2-way analysis of variance (ANOVA) with post hoc testing. Architectural difference index (ADI), a combined measure of functionally relevant structural parameters predictive of length-tension, force-generation, and excursional muscle properties was used to compare PFMs across RM, rabbit, rat, and mouse. Results RM and human PFMs were similar with respect to architecture. However, the magnitude of similarity varied between individual muscles, with the architecture of the most distinct RM PFM, iliocaudalis, being well suited for quadrupedal locomotion. Except for the pubovaginalis, RM PFMs inserted onto caudal vertebrae, analogous to all tailed animals. Comparison of the PFM complex architecture across species revealed the lowest, thus closest to human, ADI for RM (1.9), followed by rat (2.0), mouse (2.6), and rabbit (4.7). Conclusions Overall, RM provides the closest architectural representation of human PFM complex among species examined; however, differences between individual PFMs should be taken into consideration. As RM is closely followed by rat with respect to PFM similarity with humans, this less-sentient and substantially cheaper model is a good alternative for PFM studies.

Structure–function relationship of the human external anal sphincter

“…Studies utilizing a rabbit model indicate that, similar to the muscles described above, the EAS operates at L s < optimal L s [8]. However, rabbit models have not been validated for human EAS and it has previously been shown that rabbit pelvic floor muscles’ architecture is the least similar to humans among experimental animals commonly used for pelvic floor disorder research [14, 15]. The same investigators used imaging combined with anal manometry to demonstrate that EAS contractile force rises with increasing distension in human clinical studies [16].…”

“…For example, indirect clinical assessments led to the notion that the human puborectalis muscle operates at a short L s [17]. In contrast, our previous direct tissue level assessments of the human pelvic floor muscles demonstrate that the puborectalis operates at optimal L s [15]. Furthermore, direct anatomical studies enable the assessment of the individual components of the anal sphincter complex, providing a critical advantage over the indirect techniques that simultaneously measure the output of the entire complex.…”

Isolation of muscle stem cells from rat skeletal muscles

“…Additionally, architectural studies of the female pelvic floor muscles showed that rats, compared to other commonly used laboratory animals, such as rabbit and mouse, were the closest to humans in terms of muscle design (Alperin et al, 2014). Moreover, the architectural difference index of rat pelvic floor muscles, which quantifies how closely rat muscle architecture resembles human muscle architecture, was comparable to the architectural difference index of the non-human primate (Brown et al, 2010;Lieber and Brown, 1992;Stewart et al, 2017).…”

Multimodal imaging assessment and histologic correlation of the female rat pelvic floor muscles’ anatomy

“…; Stewart et al. ). Furthermore, using this model, we have discovered the existence of protective pregnancy‐induced adaptations in these muscles (Alperin et al.…”

“…The rat is the most widely used experimental model in pelvic floor disorders research. Through a comparative analysis of the human and rat PFM architecture, the main determinant of in vivo muscle function, we have previously validated the rat model with respect to PFMs (Alperin et al 2014;Stewart et al 2017). Furthermore, using this model, we have discovered the existence of protective pregnancy-induced adaptations in these muscles (Alperin et al 2015(Alperin et al , 2016.…”