scholarly journals Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)

2011 ◽  
Vol 178 (3) ◽  
pp. 1233-1244 ◽  
Author(s):  
Wei Lin ◽  
Nafis A. Rahman ◽  
Jian Lin ◽  
Hua Zhang ◽  
Kemian Gou ◽  
...  
Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5556-5565 ◽  
Author(s):  
Tristan M. Nicholson ◽  
Emily A. Ricke ◽  
Paul C. Marker ◽  
Joseph M. Miano ◽  
Robert D. Mayer ◽  
...  

Abstract Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are common in older men and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17β-estradiol (E2). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E2 (T+E2). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T+E2 developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T+E2 had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T+E2, who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T+E2 is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO.


Author(s):  
Baoyi Zhu ◽  
Zhanfang Kang ◽  
Sihua Zhu ◽  
Yuying Zhang ◽  
Xiangmao Lai ◽  
...  

Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.


2005 ◽  
Vol 173 (4S) ◽  
pp. 333-333
Author(s):  
Shaohua Chang ◽  
Joseph A. Hypolite ◽  
Alan J. Wein ◽  
Samuel Chacko ◽  
Michael E. DiSanto

2005 ◽  
Vol 173 (4S) ◽  
pp. 394-394
Author(s):  
Martha A. Hass ◽  
Robert M. Levin ◽  
William Connors ◽  
Alma Birnboim

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