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

Abramowitch, Steven D.; Feola, Andrew; Jallah, Zegbeh; Moalli, Pamela

doi:10.1016/j.ejogrb.2009.02.022

Cited by 192 publications

(164 citation statements)

References 99 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…To understand how the various risk factors for UI affect the morphological properties of striated muscle, animal models are useful because the experiments are conducted under controlled conditions. 11 The striated muscle fiber composition of the diabetic pregnant rat urethra is presented along with the importance of considering the experimental conditions and the inclusion of three control groups (virgin, pregnant and diabetic virgin). With this methodology, it was possible to separately analyze the influences of diabetes vs pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Morphological changes in the fast vs slow fiber profiles of the urethras of diabetic pregnant rats

Marini

Barbosa

Damasceno

et al. 2011

UIJ

View full text Add to dashboard Cite

Background. This study was undertaken to test the hypothesis that diabetes and pregnancy detrimentally affect the normal function of urethral striated muscles in rats, providing a model for additional studies related to urinary incontinence. The aim of this study was to evaluate morphological alterations in the urethral striated muscles of diabetic pregnant rats.Materials and Methods. Twenty female Wistar rats were distributed into four experimental groups of five rats as follows: virgin, pregnant, diabetic virgin, and diabetic pregnant. Diabetes was induced using streptozotocin administration (40 mg/kg i.v.). The rats were lethally anesthetized, and the urethra and vagina were extracted as a unit. Cryostat sections (6 µm thick) were cut and stained with hematoxylin-eosin, and immunohistochemical procedures were performed and subjected to morphological and semi quantitative analysis.Results. The urethral striated muscle from the diabetic pregnant rats presented with the following variations: thinning and atrophy, disorganization and disruption associated with the colocalization of fast and slow fibers and a steady decrease in the proportion of fast vs slow fibers.Conclusion. Diabetes and pregnancy impair the urethral striated muscle and alter its fiber type distribution.

show abstract

Section: Discussionmentioning

confidence: 99%

Morphological changes in the fast vs slow fiber profiles of the urethras of diabetic pregnant rats

Marini

Barbosa

Damasceno

et al. 2011

UIJ

View full text Add to dashboard Cite

show abstract

“…These spines often present the greatest challenges to delivery because they form the most restricted part of the birth canal, in the pelvic midplane [18]. If they are too far apart, the muscles can weaken with pregnancy and birth, contributing to pelvic organ prolapse (POP), a disorder that affects as many as 25% of women in the United States today [19][20][21]. In women with transversely wide birth canals (and potentially easier births), the risk of POP is greater than it is for women with pelves characterized by closely spaced ischial spines [18], suggesting a selective advantage of closely spaced spines that may override the advantage of large birth canals.…”

Section: Human Birth: Anatomy Evolutionary History and Modern Conseqmentioning

confidence: 99%

Primate pelvic anatomy and implications for birth

Trevathan

2015

Phil. Trans. R. Soc. B

104

View full text Add to dashboard Cite

The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an 'obstetric dilemma' whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and nonhuman primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate.

show abstract

“…[1][2][3]. Epidemiologic studies indicate that (a) vaginal birth, aging, and increased body mass index are major risk factors for the development of POP and (b) more than 1 pathology may be involved to exhibit full anatomical loss of support.…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans

Budatha¹,

Roshanravan²,

Zheng³

et al. 2011

J. Clin. Invest.

133

132

View full text Add to dashboard Cite

Pelvic organ prolapse (POP) is a common condition affecting almost half of women over the age of 50. The molecular and cellular mechanisms underlying this condition, however, remain poorly understood. Here we have reported that fibulin-5, an integrin-binding matricellular protein that is essential for elastic fiber assembly, regulated the activity of MMP-9 to maintain integrity of the vaginal wall and prevented development of POP. In murine vaginal stromal cells, fibulin-5 inhibited the β 1 integrin-dependent, fibronectin-mediated upregulation of MMP-9. Mice in which the integrin-binding motif was mutated to an integrin-disrupting motif (Fbln5 RGE/RGE ) exhibited upregulation of MMP-9 in vaginal tissues. In contrast to fibulin-5 knockouts (Fbln5 -/-), Fbln5 RGE/RGE mice were able to form intact elastic fibers and did not exhibit POP. However, treatment of mice with β-aminopropionitrile (BAPN), an inhibitor of matrix cross-linking enzymes, induced subclinical POP. Conversely, deletion of Mmp9 in Fbln5 -/-mice significantly attenuated POP by increasing elastic fiber density and improving collagen fibrils. Vaginal tissue samples from pre-and postmenopausal women with POP also displayed significantly increased levels of MMP-9. These results suggest that POP is an acquired disorder of extracellular matrix and that therapies targeting matrix proteases may be successful for preventing or ameliorating POP in women. IntroductionPelvic organ prolapse (POP) is characterized by abnormal protrusion of female pelvic organs involving the uterus, bladder, and vagina (reviewed in refs. 1-3). Epidemiologic studies indicate that (a) vaginal birth, aging, and increased body mass index are major risk factors for the development of POP and (b) more than 1 pathology may be involved to exhibit full anatomical loss of support. Although approximately 11% of women have surgery for POP or urinary incontinence in their lifetimes (4), to date, effective therapies to prevent progression of POP have not been established, thereby imposing profound social and financial burden to affected individuals (3).Despite a difference in anatomical position of pelvic organs relative to the body axis and pelvic floor, rodent models of POP have provided important tools to study underlying mechanisms of prolapse. In contrast to an observation that rectal prolapse is frequently associated with the presence of chronic inflammatory bowel disease (5), POP has been found in animals with defective ECM proteins, including fibulin-3, fibulin-5, and lysyl oxidaselike-1 (LOXL-1) (an enzyme that predominantly catalyzes crosslinking of elastin) (6-8). Interestingly, these proteins are abundantly expressed in the vaginal wall and involved in synthesis and assembly of elastic fibers. It is also known that uterosacral ligaments support the vaginal wall and that Hoxa11 is essential for formation of uterosacral ligaments in mice (9). Hoxa11-deficient mice exhibit increased mobility of the uterus; however,

show abstract

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

Cited by 192 publications

References 99 publications

Morphological changes in the fast vs slow fiber profiles of the urethras of diabetic pregnant rats

Morphological changes in the fast vs slow fiber profiles of the urethras of diabetic pregnant rats

Primate pelvic anatomy and implications for birth

Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans

Contact Info

Product

Resources

About