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A Mouse Model of Cavernous Nerve Injury-Induced Erectile Dysfunction: Functional and Morphological Characterization of the Corpus Cavernosum

Authors

  • Hai-Rong Jin MD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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    • Hai-Rong Jin and Yeun Goo Chung contributed equally to this study.

  • Yeun Goo Chung MD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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    • Hai-Rong Jin and Yeun Goo Chung contributed equally to this study.

  • Woo Jean Kim PhD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Lu Wei Zhang MD, PhD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Shuguang Piao MD, PhD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Buyankhuu Tuvshintur BS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Guo Nan Yin MS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Sun Hwa Shin BS,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Munkhbayar Tumurbaatar MD,

    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • Jee-Young Han MD, PhD,

    1. Department of Pathology, Inha University School of Medicine, Incheon, Korea
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  • Ji-Kan Ryu MD, PhD,

    Corresponding author
    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
      Jun-Kyu Suh, MD, PhD, National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd Street, Shinheung-Dong, Jung-Gu, Incheon 400-711, Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr
      Ji-Kan Ryu, MD, PhD, National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd Street, Shinheung-Dong, Jung-Gu, Incheon 400-711, Korea. Tel: 82-32-890-3505; Fax: 82-32-890-3099; E-mail: rjk0929@inha.ac.kr
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  • Jun-Kyu Suh MD, PhD

    Corresponding author
    1. National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
      Jun-Kyu Suh, MD, PhD, National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd Street, Shinheung-Dong, Jung-Gu, Incheon 400-711, Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr
      Ji-Kan Ryu, MD, PhD, National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd Street, Shinheung-Dong, Jung-Gu, Incheon 400-711, Korea. Tel: 82-32-890-3505; Fax: 82-32-890-3099; E-mail: rjk0929@inha.ac.kr
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Jun-Kyu Suh, MD, PhD, National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd Street, Shinheung-Dong, Jung-Gu, Incheon 400-711, Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr
Ji-Kan Ryu, MD, PhD, National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd Street, Shinheung-Dong, Jung-Gu, Incheon 400-711, Korea. Tel: 82-32-890-3505; Fax: 82-32-890-3099; E-mail: rjk0929@inha.ac.kr

ABSTRACT

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. Jin H-R, Chung YG, Kim WJ, Zhang LW, Piao S, Tuvshintur B, Yin GN, Shin SH, Tumurbaatar M, Han J-Y, Ryu J-K, and Suh J-K. A mouse model of cavernous nerve injury-induced erectile dysfunction: Functional and morphological characterization of the corpus cavernosum. J Sex Med 2010;7:3351–3364.

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