Functional and morphologic characterizations of the diabetic mouse corpus cavernosum: comparison of a multiple low-dose and a single high-dose streptozotocin protocols.
BACKGROUND
With the advent of genetically modified mice, it seems particularly advantageous to develop a mouse model of diabetic erectile dysfunction.


OBJECTIVE
To establish a mouse model of type I diabetes by implementation of either multiple low-dose streptozotocin (STZ) protocol or single high-dose STZ protocol and to evaluate morphologic alterations in the cavernous tissue and subsequent derangements in penile hemodynamics in vivo.


METHODS
Eight-week-old C57BL/6J mice were divided into three groups: a control group, a group administered the multiple low-dose STZ protocol (50 mg/kg x 5 days), and a group administered the single high-dose STZ protocol (200 mg/kg).


METHODS
After 8 weeks, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with hydroethidine (in situ analysis of superoxide anion), TUNEL, or antibodies to nitrotyrosine (marker of peroxynitrite formation), PECAM-1, smooth muscle alpha-actin, and phospho-eNOS. Penis specimens from a separate group of animals were used for phospho-eNOS and eNOS western blot or cGMP determination.


RESULTS
Erectile function was significantly less in diabetic groups than in control group. The generation of superoxide anion and nitrotyrosine and the number of apoptotic cells in both cavernous endothelial and smooth muscle cells were significantly higher in diabetic groups than in control group. Cavernous tissue phospho-eNOS and cGMP expression and the number of endothelial and smooth muscle cells were lower in diabetic groups than in control group. Both diabetic models resulted in similar structural and functional derangements in the corpus cavernosum; however, the mortality rate was higher in mice receiving single high-dose of STZ than in those receiving multiple low-doses.


CONCLUSIONS
The mouse model of type I diabetes is useful and technically feasible for the study of the pathophysiologic mechanisms involved in diabetic erectile dysfunction.
Jin
Hai-Rong
HR
National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
Kim
Woo Jean
WJ
Song
Jae Sook
JS
Choi
Min Ji
MJ
Piao
Shuguang
S
Shin
Sun Hwa
SH
Tumurbaatar
Munkhbayar
M
Tuvshintur
Buyankhuu
B
Nam
Moon-Suk
MS
Ryu
Ji-Kan
JK
Suh
Jun-Kyu
JK
D000818:Animals; D002985:Clinical Protocols; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003922:Diabetes Mellitus, Type 1; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007172:Erectile Dysfunction / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D005240:Feasibility Studies; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D010413:Penis / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D013311:Streptozocin / Q000008:administration & dosage
D013311:Streptozocin