Pelvic organ prolapse is a vaginal protrusion of female pelvic organs. It has high prevalence worldwide and represents a great burden to the economy. The pathophysiology of pelvic organ prolapse is multifactorial and includes genetic predisposition, aberrant connective tissue, obesity, advancing age, vaginal delivery and other risk factors. Owing to the long course prior to patients becoming symptomatic and ethical questions surrounding human studies, animal models are necessary and useful. These models can mimic different human characteristics -histological, anatomical or hormonal, but none present all of the characteristics at the same time. Major animal models include knockout mice, rats, sheep, rabbits and nonhuman primates. In this article we discuss different animal models and their utility for investigating the natural progression of pelvic organ prolapse pathophysiology and novel treatment approaches. Keywordsaberrant connective tissue; animal model; female; mesh repair; pelvic organ prolapse; POP; vaginal delivery Pelvic organ prolapse (POP) consists of descent of the anterior, posterior or apical vaginal compartments. While not life-threatening, POP often results in a significant reduction in quality of life, including shame, embarrassment and sexual dysfunction. POP is also a significant economic burden to millions of women and the healthcare system since it is one of the major indications for benign gynecological surgery, accounting for over 225,000 inpatient procedures and costing more than US$1 billion per year in the USA alone [1].The pathophysiology of POP is still not well understood, but is known to involve genetic predisposition, aberrant connective tissue (CT) metabolism, pregnancy and hormonal effects, vaginal delivery, and other risk factors such as previous hysterectomy, obesity, advancing age and constipation [1]. POP often develops decades after the greatest risk © 2012 Expert Reviews Ltd * Author for correspondence: Tel.: + 1 216 444 1103, Fax: + 1 216 444 9198, damasem@ccf.org. Financial & competing interests disclosureThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NIH Public Access Author ManuscriptExpert Rev Obstet Gynecol. Author manuscript; available in PMC 2013 March 01. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript factor, vaginal delivery, suggesting an additional impact of aging. Given the long time course and the complex and multifaceted nature of this disorder, animal models are a potentially useful way to improve our understanding of POP.Animal models are particularly appropriate for studying the natural progression of pathologies and investigating novel treatment approaches. However, the development of applicable animal models for POP is challenging since humans, as t...

A significant number of women experience stress urinary incontinence (SUI), which greatly affects their quality of life. Recent research investigating utilization of stem cells and their derivatives for the prevention and treatment of SUI has been performed to test the effect of cell source and method of administration in several animal models of SUI. The type of stem cell, timing of optimal dose or doses after injury, mechanism of action of stem cells, and route of administration must be investigated both preclinically and clinically before stem cell therapy becomes a possible treatment for SUI, although the future of this therapy looks promising. This article reviews the progress in stem cell research for incontinence and describes areas of future work as suggested by research in other fields.

Objectives Lysyl oxidase-like 1 knockout (Loxl1−/−) mice demonstrate deficient elastin homeostasis associated with pelvic organ prolapse (POP). To further investigate the pathophysiology of POP in these animals, a genetically-matched homozygous positive (Loxl1+/+) or wild type strain is needed. This study sought to create and validate genetically-matched Loxl1+/+ and Loxl1−/− strains. Methods Female Loxl1−/− mice were backcrossed with male wild-type mice. The resultant heterozygous mice were bred to produce Loxl1+/+ and Loxl1−/− mice, whose genotype was confirmed by RT-PCR. Multiparous female Loxl1−/− (n=7) and Loxl1+/+ (n=9) mice were assessed for POP weekly for 12 weeks after their first vaginal delivery. POP was compared between groups using a Kaplan Meier survival curve with p<0.05 indicating a significant difference. Vaginal connective tissue (CT) histology was assessed qualitatively and quantitatively. Results There were no significant differences between the groups in age or parity. Four of 7 Loxl1−/− mice developed prolapse by 8 weeks and 6 of 7 by 12 weeks post-partum. No Loxl1+/+ mouse prolapsed. Loxl1−/− mice had significantly larger vaginas as determined by area within the lumen and total cross-sectional tissue area. Striated muscle fibers of the urethra in Loxl1−/− mice were less organized, shorter, and thinner than in Loxl1+/+ mice. Conclusions Genetically-matched Loxl1−/− and Loxl1+/+ strains can be reliably created by a backcross method and differentiate in their prolapse phenotype. Loxl1−/− mice demonstrate pathology primarily characterized by enlargement of the vagina. Further studies are needed to elucidate the cause of this finding.

Aims: Urodynamics (UDS) is widely used for the diagnosis of lower urinary tract dysfunction. Air-Charged catheters (ACC), one of the newer technologies for UDS pressure recording, has been adopted in growing numbers around the world for the past 15 years. Currently, there is a lack of published studies characterizing specific performance of the ACC. Since linearity, hysteresis, pressure drift, and frequency response are important components in characterizing accuracy for cathetermanometer systems; this study aimed to assess these four aspects in ACC. Methods: A total of 180 T-DOC® ACC were used in three different laboratory settings to assess pressure linearity and hysteresis (15 dual-sensor vesical and urethral and 30 single-sensor abdominal), pressure drift over 2 h (115 single-sensor), and frequency response (20 single-sensor). Data are presented as mean ± standard deviation. Results: ACC showed linearity of 0.99 ± 0.01, 0.99 ± 0.01, and 1.01 ± 0.01; and hysteresis of 0.57 ± 0.3%, 0.76 ± 0.48%, and 1 ± 0.89% for the abdominal, vesical, and urethral sensors, respectively. A pressure drift of 2.2 ± 1.4% at 1 h and 4.4 ± 2.5% at 2 h were observed when compared to baseline pressures. The catheters did not show any amplification factor during the sweep from 1 to 30 Hz, and recorded signals up to 5 Hz attenuating higher frequency signals. Conclusions:In this study the T-DOC® ACC showed a linear performance with minimal hysteresis associated with acceptable pressure drift, and adequate frequency response to capture clinically relevant pressures. The accurate results observed in this study suggest that these catheters are technically suitable to be used as a measuring instrument for UDS.

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Abstract Pelvic organ prolapse (POP) in lysyl oxidase like-1 knockout (Loxl1 KO) mice occurs primarily in parous mice and is rare in nulliparous mice. We determined the effect of Loxl1 deficiency on postpartum regulation of connective tissue metabolism genes and degradative enzyme activity in the vagina at 20 days gestation or 4 h, 48 h, 7 days, 15 days, 25 days, 7 weeks, or 12 weeks postpartum. Nulliparous Loxl1 KO and wildtype (WT) mice aged 11, 18, or 23 weeks were controls. Gene expression and enzyme activity were assessed using real-time quantitative reverse transcription PCR and fluorescein conjugated gelatin zymography, respectively. Parity, but not aging, had a significant influence on gene expression both with time postpartum and between KO and WT mice. Mmp2, Timp1, Timp2, Timp3, Timp4, Col1a1, Col3a1, Acta2, and Bmp1 were differentially expressed between KO and WT mice. Correlational analysis of gene-gene pairs revealed 10 significant differences between parous KO and WT groups, 5 of which were due to lack of co-expression of Bmp1 in KO mice. The overall enzyme activity that could be attributed to MMPs was significantly higher in WT compared to KO mice both 25 days and 12 weeks postpartum, and MMP activity was significantly lower 15 days and 25 days postpartum compared to KO nulliparous controls, but not WT. These findings suggest that Loxl1 deficiency combined with parity has a significant impact on postpartum regulation of connective tissue metabolism, particularly as it relates to co-expression of Bmp1 and altered proteolytic activity.

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