The human penis is an organ with a unique anatomy that does not have a perfect homologous in the animal kingdom, much less among the animals commonly used to model disease. Researchers hypothesize that the lack of good representative models is one of the main causes why advances in preclinical studies are not being translated to standard healthcare [1]. 
The focus of our research is urethral reconstruction for treatment of congenital or acquired male urethral diseases. Reconstructive surgery depends on availability of local tissue or autologous graft material and in case of shortness of both of these, tissue engineering may be a solution [2].
Animal models are used to extrapolate experimental data to human clinical practice. It is necessary to understand the strengths and limitations of these animal models and to use animal models wisely and with caution. Here we study literature for animals used as a model for male urethral surgery, in order to understand the similarities and disparities between humans and animal models with a clear focus on anatomy. This knowledge will contribute to the use of the right animal model in testing new graft materials and new surgical technology.

A literature search for articles published in English was performed using a PubMed database search for articles published in the past three decades in the period ending November 2021. The search keywords used were “urethra,” “animal model,” “urethral disease,” "anatomy," and “preclinical studies”. The authors reviewed the selected articles, and their findings/conclusions were incorporated into the manuscript. Exclusion criteria were foreign language, female urethra and endoscopic surgery.

We compared mouse, rat, rabbit, dog, pig, ruminants and primate penile anatomy and urethral development. Despite the evident morphologic variations when it comes to embryonic development, in most animals the development of the urethra is similar to human. In contrast to the correspondence between urethras, penile morphology is remarkably different from human. Rodents (mouse and rat) as well as dogs have a bone in the glans, the os penis, whereas in pigs the penis is contained in a preputial space close to the abdomen. Moreover, the pig’s penis has sigmoid flexure and corkscrew shaped tip. In ruminants (ram and goat), only corpus cavernosum is recognized, while corpus spongiosum is lacking. Lastly, primate penises vary in length, complexity and specializations (lumps, flanges, ridges), specific for each species. Rabbit penis is bigger than rodents’ and belongs to the vascular type, comparable with the human penis. In vascular penises, erection is a consequence of size increasing and organ hardening, while in fibroelastic penises, e.g. in dogs and pigs, erection involves mainly increase of length.

Although the urethra of male pigs largely resembles the urethra in men, shape of the penis of the pig is very different. The major disadvantage of ruminants is that the corpus spongiosum is lacking, while in human urethral diseases the involvement of spongious tissue is relevant. Dogs differ from humans in having a penile bone, and maybe of more importance is that their use as a model is largely influenced by ethical and emotional culture attachment to these animals as pets. Both dog and pig are expensive to host, if not using mini pig the Yorkshire pig grow very fast, and can cause difficulties when kept in a group of males. That is one of the reasons why for most dog studies females species are used instead of male. 
Overall, there is not a perfect animal model that can give urethral tissue engineering new approaches a boost to the clinic, since human penis has a unique anatomy with no accurate homologous in nature. Nevertheless, among the available animal models, we propose the use of rabbits. Balance between responsible animal experimentation and reasonably good translation to clinic is found in rabbit penis and urethra. 
Limitations of our study are that urine composition and cell culture of the urogenital cells have not been taken into account.

The rabbit urethra and penis have the most similarities with the human urethra and penis, including spongious tissue and without a penile bone. Furthermore, the rabbit penis is large enough for surgery. In this respect, we suggest the rabbit penis as the model of choice for experimental urethral surgery, but other animal models may have a place for specific aims.

Versteegden, L.R.M., et al., Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies. Eur Urol, 2017. 72(4): p. 594-606.
Atala, A., Experimental and clinical experience with tissue engineering techniques for urethral reconstruction. Urol Clin North Am, 2002. 29(2): p. 485-92, ix