Tunica albuginea allograft: a new model of LaPeyronie's disease with penile curvature and subtunical ossification

Abstract

The pathophysiology of LaPeyronie's disease (PD) is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excision with subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat's tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograft, and both collagen-II- and osteocalcin-positive cells were also noted. Tunica albuginea (TA) allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.

Figure 1

Surgical procedure. (a) tunica albuginea resection; (b) aspect after allografting; (c) aspect at 12 weeks during artificially induced erection. CC: corpus cavernosum; CS: corpus spongiosum. The grafted area is localized by an ellipsis. *: suture.

Figure 2

Statistical analysis. (a) penile curvature was significantly observed at every time point in allografted groups compared to control group (ANOVA). (b) erectile function was not significantly different compared to control group. ICP: intra cavernous pressure; MAP: mean arterial pressure.

Figure 3

Elastic fiber analysis. (a) control (autografted tunica), (b) allografted tunica, (c) elastic fiber length was significantly decreased in allografted tunica compared to normal tunica (P < 0.0001; Mann-Whitney). Elastic fibers are designed by arrows. Hart staining. Scale bars = 40 μm.

Figure 4

(a): Trichrome staining 1 weeks after allograft; (b) after 3 weeks; (c) after 7 weeks, (d) after 12 weeks (×20 magnification); (e–h): ×200 magnification of (a–d) area of interest.

Figure 5

Immunohistochemistry and histochemistry. (a): TGF-β1 (×1000); (b): SMAD 2 (×400); (c): von Kossa staining showing calcium salts (×400); (d): Collagen II (×200); (e): osteocalcin (×400); (f): CD 3 (×100); (g): CD 45 (×200). Positive staining is designated by arrows. (a’), (b’), (c’), (d’), (e’): negative control for TGF-β1, SMAD 2, Von Kossa, Collagen II and Osteocalcin, respectively.