A mouse model of cavernous nerve injury-induced erectile dysfunction: functional and morphological characterization of the corpus cavernosum.
BACKGROUND
With the advent of genetically engineered mice, it seems important to develop a mouse model of cavernous nerve injury (CNI).


OBJECTIVE
To establish a mouse model of CNI induced either by nerve crushing or by neurectomy and to evaluate time-dependent derangements in penile hemodynamics in vivo and subsequent histologic alterations in the cavernous tissue.


METHODS
Twelve-week-old C57BL/6J mice were divided into 4 groups (N=36 per group): control, sham operation, bilateral cavernous nerve crush, and bilateral cavernous neurectomy group.


METHODS
Three days and 1, 2, 4, 8, and 12 weeks after CNI, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and TUNEL was performed. Immunohistochemical analysis was performed assaying for caspase-3, transforming growth factor-β1 (TGF-β1), phospho-Smad2, PECAM-1, factor VIII, and smooth muscle α-actin. The numbers of apoptotic cells and phospho-Smad2-immunopositive cells in endothelial cells or smooth muscle cells were counted.


RESULTS
Erectile function was significantly less in the cavernous nerve crushing and neurectomy groups than in the control or sham group. This difference was observed at the earliest time point assayed (day 3) and persisted up to 4 weeks after nerve crushing and to 12 weeks after neurectomy. The apoptotic index peaked at 1 or 2 weeks after CNI and decreased thereafter. Cavernous TGF-β1 and phospho-Smad expression was also increased after CNI. The numbers of apoptotic cells and phospho-Smad2-immunopositive cells in cavernous endothelial cells and smooth muscle cells were significantly greater in the cavernous nerve crush and cavernous neurectomy groups than in the control or sham group. Conclusion.  The mouse is a useful model for studying pathophysiologic mechanisms involved in erectile dysfunction after CNI. Early intervention to prevent apoptosis in smooth muscle cells and endothelial cells or to inhibit cavernous tissue fibrosis is required to restore erectile function.
Jin
Hai-Rong
HR
National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
Chung
Yeun Goo
YG
Kim
Woo Jean
WJ
Zhang
Lu Wei
LW
Piao
Shuguang
S
Tuvshintur
Buyankhuu
B
Yin
Guo Nan
GN
Shin
Sun Hwa
SH
Tumurbaatar
Munkhbayar
M
Han
Jee-Young
JY
Ryu
Ji-Kan
JK
Suh
Jun-Kyu
JK
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000293:injuries / Q000294:innervation* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D053773:Transforming Growth Factor beta1