TY - JOUR
T1 - A mouse model of cavernous nerve injury-induced erectile dysfunction
T2 - Functional and morphological characterization of the corpus cavernosum
AU - Jin, Hai Rong
AU - Chung, Yeun Goo
AU - Kim, Woo Jean
AU - Zhang, Lu Wei
AU - Piao, Shuguang
AU - Tuvshintur, Buyankhuu
AU - Yin, Guo Nan
AU - Shin, Sun Hwa
AU - Tumurbaatar, Munkhbayar
AU - Han, Jee Young
AU - Ryu, Ji Kan
AU - Suh, Jun Kyu
N1 - Funding Information:
This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (R0A-2007-000-20018-0, Jun-Kyu Suh). The authors thank Jennifer Holmes for help in preparing the manuscript.
PY - 2010/10
Y1 - 2010/10
N2 - Introduction.: With the advent of genetically engineered mice, it seems important to develop a mouse model of cavernous nerve injury (CNI). Aim.: 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. Main Outcome Measures.: 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.
AB - Introduction.: With the advent of genetically engineered mice, it seems important to develop a mouse model of cavernous nerve injury (CNI). Aim.: 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. Main Outcome Measures.: 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.
KW - Animal Model
KW - Erectile Dysfunction
KW - Mouse
KW - Radical Prostatectomy
UR - http://www.scopus.com/inward/record.url?scp=77957351998&partnerID=8YFLogxK
U2 - 10.1111/j.1743-6109.2010.01942.x
DO - 10.1111/j.1743-6109.2010.01942.x
M3 - Article
C2 - 20646178
AN - SCOPUS:77957351998
SN - 1743-6095
VL - 7
SP - 3351
EP - 3364
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
IS - 10
ER -