Pathology of urethral fibromuscular system related to parturition-induced stress urinary incontinence and TGF-β1/Smad pathway.
To study pathological changes of fibromuscular system and the role of TGF-β1/Smad pathway in the urethra of a parturition-induced stress urinary incontinence (SUI) rat model. Twenty-eight 8-week-old Sprague-Dawley female rats at gestational day 16 were used and randomized into two groups: sham group and SUI group. After delivery, rats in the SUI group underwent postpartum vaginal balloon dilation and bilateral ovariectomy. 1 month after ovariectomy, urodynamics was assessed. Histological examination (Masson's trichrome stain, picrosirius red stain, Hart's elastin stain, Gordon & Sweet's stain, and immunohistochemical stain) and Western blot were performed on urethral tissues. Both leak point pressure and maximal bladder capacity were significantly decreased in the balloon-injured ovariectomized rats, compared with the sham rats. Muscle was significantly decreased in the urethra of SUI rats compare with sham rats. Collagen I/III and reticular fibers from SUI group were also significantly lower than sham group. Meanwhile, elastic fibers and reticular fibers showed fragmentation and disorganization indicating impairment in the fibromuscular system in SUI rats. TGF-β1, MMP-9, and phosphorylated Smad2 (p-Smad2) were expressed significantly higher in SUI than in sham rats. Simulated birth trauma and menopause induced an upregulation of the TGF-β1/Smad pathway and impairment of the fibromuscular system in the urethra.
Andrology Center, Peking University First Hospital, Beijing 100034, China.
Guang-Yong
GY
Li
Wan-Shou
WS
Cui
Feng
F
Zhou
Zhe-Zhu
ZZ
Gao
Hua
H
Xin
Tao
T
Liu
Wei-Ren
WR
Li
Yan-Qing
YQ
Gong
Guang-Yi
GY
Bai
Ying-Lu
YL
Guo
Zhong-Cheng
ZC
Xin
D000818:Animals; D001720:Birth Injuries; D002404:Catheterization / Q000009:adverse effects; D004547:Elastic Tissue / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009139:Musculoskeletal Abnormalities / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects; D036801:Parturition; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014521:Urethra / Q000293:injuries / Q000473:pathology*; D014550:Urinary Incontinence, Stress / Q000235:genetics / Q000378:metabolism*; D014563:Urodynamics / Q000502:physiology; D014621:Vagina / Q000293:injuries / Q000378:metabolism
D051899:Smad2 Protein; C497784:Smad2 protein, rat; D053773:Transforming Growth Factor beta1; D020780:Matrix Metalloproteinase 9