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      Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content

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          Abstract

          Pelvic organ prolapse (POP) is characterised by the weakening of the pelvic floor support tissues, and often by subsequent prolapse of the bladder outside the body, i.e. cystocele. The bladder is kept in place by the anterior vaginal wall which consists of a dense extracellular matrix rich in collagen content that is maintained and remodelled by fibroblastic cells, i.e. fibroblasts and myofibroblasts. Since altered matrix production influences tissue quality, and myofibroblasts are involved in normal and pathological soft tissue repair processes, we evaluated matrix production of cells derived from pre- and post-menopausal POP and non-POP control anterior vaginal wall tissues. Results showed that cells from postmenopausal POP women deposited matrices with high percentage of collagen fibres with less anisotropic orientation and increased stiffness than those produced by controls. There was a transient increase in myofibroblastic phenotype that was lost after the peak of tissue remodelling. In conclusion, affected fibroblasts from postmenopausal prolapsed tissues produced altered matrices in vitro compared to controls. Such aberrant altered matrix production does not appear to be a consequence of abnormal phenotypical changes towards the myofibroblastic lineage.

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          Pelvic organ prolapse.

          Pelvic organ prolapse is downward descent of female pelvic organs, including the bladder, uterus or post-hysterectomy vaginal cuff, and the small or large bowel, resulting in protrusion of the vagina, uterus, or both. Prolapse development is multifactorial, with vaginal child birth, advancing age, and increasing body-mass index as the most consistent risk factors. Vaginal delivery, hysterectomy, chronic straining, normal ageing, and abnormalities of connective tissue or connective-tissue repair predispose some women to disruption, stretching, or dysfunction of the levator ani complex, connective-tissue attachments of the vagina, or both, resulting in prolapse. Patients generally present with several complaints, including bladder, bowel, and pelvic symptoms; however, with the exception of vaginal bulging, none is specific to prolapse. Women with symptoms suggestive of prolapse should undergo a pelvic examination and medical history check. Radiographic assessment is usually unnecessary. Many women with pelvic organ prolapse are asymptomatic and do not need treatment. When prolapse is symptomatic, options include observation, pessary use, and surgery. Surgical strategies for prolapse can be categorised broadly by reconstructive and obliterative techniques. Reconstructive procedures can be done by either an abdominal or vaginal approach. Although no effective prevention strategy for prolapse has been identified, considerations include weight loss, reduction of heavy lifting, treatment of constipation, modification or reduction of obstetric risk factors, and pelvic-floor physical therapy.
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            Tissue mechanics, animal models, and pelvic organ prolapse: a review.

            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.
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              On the biomechanics of vaginal birth and common sequelae.

              Approximately 11% of U.S. women undergo surgery for pelvic floor dysfunction, including genital organ prolapse and urinary and fecal incontinence. The major risk factor for developing these conditions is giving vaginal birth. Vaginal birth is a remarkable event about which little is known from a biomechanical perspective. We first review the functional anatomy of the female pelvic floor, the normal loads acting on the pelvic floor in activities of daily living, and the functional capacity of the pelvic floor muscles. Computer models show that the stretch ratio in the pelvic floor muscles can reach an extraordinary 3.26 by the end of the second stage of labor. Magnetic resonance images provide evidence that show that the pelvic floor regions experiencing the most stretch are at the greatest risk for injury, especially in forceps deliveries. A conceptual model suggests how these injuries may lead to the most common form of pelvic organ prolapse, a cystocele.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                11 March 2016
                2016
                : 6
                : 22971
                Affiliations
                [1 ]Department of Orthopedic Surgery, VU University medical center, Research Institute MOVE, Netherlands Institute for Regenerative Medicine , Amsterdam, The Netherlands
                [2 ]Department of Oral Cell Biology, ACTA- University of Amsterdam and VU University, Research Institute MOVE , Amsterdam, The Netherlands
                [3 ]TNO Metabolic Health Research , Leiden, The Netherlands
                Author notes
                [*]

                Present address: Department of Obstetrics and Gynecology, and Department of Urology, Radboud University Medical Center, Geert Grooteplein Zuid 26-28 (route 267, room 1.75), 6525 GA Nijmegen, The Netherlands.

                Article
                srep22971
                10.1038/srep22971
                4786799
                26965792
                ff5ef1eb-e2f1-48d4-83d8-4b30b61389c7
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 30 November 2015
                : 22 February 2016
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