Lee Una J, Gustilo-Ashby A Marcus, Daneshgari Firouz, Kuang Mei, Vurbic Drina, Lin Dan Li, Flask Chris A, Li Tiansen, Damaser Margot S
Glickman Urological and Kidney Institute, Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH, USA.
Am J Physiol Renal Physiol. 2008 Aug;295(2):F545-55. doi: 10.1152/ajprenal.00063.2008. Epub 2008 May 21.
Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.
女性盆底功能障碍（FPFD）是一组复杂的病症，包括尿失禁和盆腔器官脱垂（POP）。在人类中，弹性蛋白稳态与FPFD的病理生理学有关。赖氨酰氧化酶样1基因敲除（LOXL1-KO）小鼠表现出异常的弹性纤维稳态，并在产后出现FPFD。我们比较了有和没有POP的LOXL1-KO小鼠的下尿路（LUT）解剖结构和功能。在28周以上的LOXL1-KO小鼠中评估LUT解剖结构。使用7特斯拉磁共振成像（MRI）扫描仪评估LOXL1-KO小鼠的盆腔内脏解剖结构。使用清醒膀胱测压和漏点压力（LPP）测试评估LUT功能。对尿道外括约肌（EUS）横截面进行弹性纤维的定量组织学分析。到25周龄时，50%的经产LOXL1-KO小鼠出现POP。与没有POP的小鼠相比，患有POP的LOXL1-KO小鼠在MRI上膀胱的大小和位置变异性更大。经产和POP与较低的LPP相关。在患有POP的LOXL1-KO小鼠的EUS中，弹性蛋白簇显著增加。由于经产会引发LOXL1-KO小鼠出现POP，患有POP的LOXL1-KO小鼠盆腔内部解剖结构存在差异，并且经产和POP均与LPP降低相关，我们得出结论，LOXL1的LUT解剖和功能表型类似于人类的FPFD。患有POP的LOXL1-KO小鼠尿道中弹性蛋白簇的增加表明弹性蛋白紊乱可能导致功能异常。我们得出结论，LOXL1在FPFD的病理生理学方面值得进一步研究。
