Tissue mechanics, animal models, and pelvic organ prolapse: A review

Abstract

Pelvic floor disorders such as pelvic organ prolapse, urinary incontinence, and fecal incontinence affect a large number of women each year. The pelvic floor can be thought of as a biomechanical structure due to the complex interaction between the vagina and its supportive structures that are designed to withstand the downward descent of the pelvic organs in response to increases in abdominal pressure. Although previous work has highlighted the biochemical changes that are associated with specific risk factors (i.e. parity, menopause, and genetics), little work has been done to understand the biomechanical changes that occur within the vagina and its supportive structures to prevent the onset of these pelvic floor disorders. Human studies are often limited due to the challenges of obtaining large tissue samples and ethical concerns. Therefore, it is necessary to investigate the use of animal models and their importance in understanding how different risk factors affect the biomechanical properties of the vagina and its supportive structures. In this review paper, we will discuss the different animal models that have been previously used to characterize the biomechanical properties of the vagina: including non-human primates, rodents, rabbits, and sheep. The anatomy and preliminary biomechanical findings are discussed along with the importance of considering experimental conditions, tissue anisotropy, and viscoelasticity when characterizing the biomechanical properties of vaginal tissue. Although there is not a lot of biomechanics research related to the vagina and pelvic floor, the future is exciting due to the significant potential for scientific findings that will improve our understanding of these conditions and hopefully lead to improvements in the prevention and treatment of pelvic disorders.

Introduction

Pelvic floor disorders comprise a wide spectrum of interrelated clinical conditions including pelvic organ prolapse, urinary incontinence, fecal incontinence, voiding dysfunction, defecatory dysfunction, and sexual dysfunction [1]. In addition to the physical symptoms that accompany these disorders, they also have a substantial emotional impact resulting in psychosocial distress that includes social isolation, anxiety, and depression [2], [3], [4]. Pelvic floor disorders affect nearly one-third of premenopausal women and nearly half of postmenopausal women [5], [6]. Each year, an estimated 135,000 women undergo surgery for urinary incontinence [7] and 225,000 women undergo surgery for pelvic organ prolapse in the United States [8], [9]. The cumulative incidence of a primary operation for pelvic organ prolapse or related condition by age 80 is 11.1%, with a direct cost of over $1 billion dollars annually in the United States [5], [7], [8], [9].

Since direct support to the pelvic organs (urethra, bladder, uterus and rectum) is provided by the vagina and indirectly by the structures involved in vaginal support [10], [11], [12], it is generally thought that damage to any component of this complex support mechanism can result in loss of vaginal support and prolapse of the pelvic organs. This concept is largely based on epidemiologic data that suggests that vaginal delivery is the greatest independent risk factor for the development of pelvic floor disorders [13], [14], [15], [16], [17]. Transient and long-term injury to the vagina and its supportive tissues has also been documented following vaginal delivery, and most parous women have some anatomical evidence of disrupted support [18], [19], [20]. However, the majority of parous women never progress to symptomatic prolapse and those that do progress, often do not develop symptoms until years or even decades later. These observations have led to the speculation that additional factors, beyond vaginal birth, negatively impact the vagina and its supportive tissues resulting in further deterioration and prolapse progression. Other known/suggested risk factors include menopause, obesity, age, prior surgery, and a genetic predisposition [14], [16], [17], [21].

The field of urogynecology is a relatively young specialty compared to disciplines such as orthopaedic and cardiovascular surgery. The latter disciplines have had the unique opportunity to mature along side the growing field of biomechanics, which started to gain significant clinical recognition in the 1960s [22]. Biomechanics is the application of mechanics (i.e. concepts of force, motion, stress, deformation, etc.) to biological systems. Biomechanics research has helped to provide a more thorough understanding of normal tissue function, the effect of pathology, and the impact of treatment in a variety of body systems. Thus, the clinical disciplines that have embraced biomechanics have undergone significant changes in the clinical management of patients over the last few decades. As urogynecology begins to mature, it is beginning to recognize the potential benefits of rigorous biomechanics research in terms of improving the care of women. Much can be learned by simply translating and adapting concepts, techniques, and approaches that have already been established in other fields to the study of pelvic floor disorders. Of course the details may be different due to the relative complexity of the pelvic floor and the enormous changes it must undergo throughout the reproductive cycle; yet, many of the same concepts can still be applied as the pelvic floor is inherently a load bearing structure that must respond to physiologic forces and undergo significant deformation similar to many other tissues. In this way, a biomechanical perspective can help us to more clearly define what constitutes normal function of the pelvic floor, the changes related to pathology, and the impact of treatment. By doing so, the application of biomechanics will undoubtedly lead to changes in the management of urogynecological disorders in the same way it has done for vascular and orthopedic problems [23], [24].

While there is clearly much to learn regarding the biomechanics of the pelvic floor, a lack of significant progress thus far can at least be partially attributed to the difficultly of performing controlled, longitudinal studies in human patients along with the ethical issues surrounding the procurement of human tissue. This can be especially problematic in biomechanics research since larger tissue samples are frequently required to perform experiments appropriately. Animal models, on the other hand, afford the opportunity to test hypotheses more rigorously in a controlled environment. In addition, by using an appropriate model, it is possible to test the research in healthy subjects in order to dissect out differences due to a specific variable in question. Moreover, animals provide significantly improved access to tissue such that more detailed biomechanical experiments can be performed.

Of course, there is no perfect substitute for humans. Thus, the choice of a specific animal model is largely driven by the research question under investigation. These decisions should be based on a defined set of scientific and ethical criteria. However, with very little data available on the biomechanical behavior of animal models related to vaginal and pelvic floor function, the choice of a specific animal model can be difficult. Thus, the goal of this article is to provide a review of the animal models used in studies of the vagina and pelvic floor, which to date include non-human primates, sheep, rabbits, and rodents. We will first discuss gross anatomical similarities and differences between these animals relative to humans. We will then condense the available information on the histomorphology and biochemistry of the vagina; before providing an overview of biomechanics research related to the vagina and pelvic floor and how animal models are being used to improve our biomechanical perspective. Finally, we will conclude by discussing future areas for biomechanics research and the potential role of animal models in these studies.

It is our hope that this review will serve to educate both current and future pelvic floor scientists and surgeons regarding the appropriateness of different animal models for biomechanical testing of the vagina and its supportive tissues, so as to assist them in making informed research decisions in the future. In addition, it is our hope that the ethical and appropriate use of animals for biomechanical studies will aid in the progression of pelvic floor research, which is imperative for protecting the health and well-being of women.