In males, androgens, in particular testosterone, are known to have many important physiological actions, including effects on muscle, bone, central nervous system, prostate, bone marrow, and sexual function. There are many causes of a bilateral loss or congenital absence of the testicles, which compromises endocrine, reproductive, and psychological function in men. The testes can be congenitally absent in conditions such as unresolved cryptorchidism due to bilateral maldescent or atrophy. Acquired causes of anorchia include trauma, torsion, toxic damage from alcohol or chemotherapy and infections, such as mumps, orchitis or bilateral orchiectomy, which may be performed as a treatment for primary testicular cancer. There are many sequelae for patients without testes. Patients are sterile, have increased risk of osteoporosis and pathologic fractures, and are subject to further complications, such as sexual dysfunction, mood changes, severe psychological trauma, altered fat distribution, reduced stamina, and muscle wasting [28].

Current strategies of treatment in anorchic patients focus on the medical management of androgenic hormone replacement therapy to avoid the complications associated with hypogonadism. And such therapy may increase muscle strength, stabilize bone density, improve osteoporosis, and restore secondary sexual characteristics, including libido and erectile function. Surgically, the main intervention is the implantation of a prosthetic testis, a procedure which is well accepted by patients and has been shown to subjectively improve body image [29].

The testes are two glandular organs, which secrete the semen, suspended in the scrotum by the spermatic cords. In mammals, the testes are located outside the body because spermatogenesis in mammals is more efficient at a temperature somewhat less than the core body. When the temperature needs to be lowered, the cremasteric muscle relaxes and the testicles are lowered away from the warm body and are able to cool.

The tunica albuginea has smooth muscle cells that course through predominantly collagenous tissue. These smooth muscle cells may impart contractile capability to the capsule, may affect blood flow into the testis, and promote the flow of seminiferous tubule fluid out of the testis.

Under the tunica albuginea, a tough fibrous shell, the testis contains very fine coiled tubes called seminiferous tubules. The tubes are lined with a layer of cells that, from puberty into old age, performed spermatogenesis.

From the cellular point of view the human testis is a complex organ comprising germ cells and a variety of somatic cells such as Sertoli, Leydig, endothelial, fibroblast, macrophage, and peritubular myoid cells.

Testicles are components of both the reproductive system (being gonads) and the endocrine system (being endocrine glands). The testis has two functions: The first is spermatogenesis, which occurs in the seminiferous tubules. The seminiferous tubules consist of germ cells and supporting cells and are a unique environment for gamete production. Support cells include the Sertoli cells and fibrocyte and myoid cells of the basement membrane. The germ cells include a slowly dividing stem cell population, more rapidly proliferating spermatogonia and spermatocytes, and metamorphosing spermatids. Sertoli cells have irregularly shaped nuclei, prominent nucleoli, low mitotic index, and exhibit unique tight junctional complexes between adjacent Sertoli cells. These tight junctions are the strongest intercellular barriers in the body. They divide the seminiferous tubule space into basal (basement membrane) and adluminal (lumen) compartments. This anatomic arrangement forms the basis for the “blood-testis barrier” and allows spermatogenesis to occur in an immunologically privileged site. Sertoli cells serve as “nurse” cells for spermatogenesis, nourishing developing germ cells that are arranged between Sertoli cell cytoplasmic projections.

The second functions of testis are secretion of steroid hormones (androgens) by Leydig cells in the interstitial tissue. Testosterone blood levels change dramatically during human fetal, neonatal, and adult life. A testosterone peak occurs in the human fetus between 12 and 18 weeks of gestation. Another testosterone peak occurs at approximately 2 months of age. A third testosterone peak occurs during the 2nd or 3rd decade of life. After this, there is a plateau, and then a slow decline with age. The testosterone peaks correspond temporally to the following developmental events: (1) the differentiation and development of the fetal reproductive tract, (2) the neonatal organization or imprinting of androgen-dependent target tissues, (3) the masculinization of the male at puberty, and (4) the maintenance of growth and function of androgen-dependent organs in the adult.

Testicular transplantation had its foundation not as a treatment modality for the recognized complications of anorchism, but for arguably less ethical reasons. The origins emerged from the quest to find the fountain of eternal youth; in this pursuit, the science of endocrinology and experimentation with testicular transplants began in the late nineteenth century. The French physiologist Charles-Édouard Brown-Séquard [30] presented the results of an experiment about injecting himself with crushed testicular extracts from young dogs and guinea pigs. He reported this technique successfully made him feel younger, along with increasing his sexual potency and heightening his intellect. This early work reinforced the belief that youth rejuvenation could be achieved through the replacement of endogenous substances, which then led to an increased interest in sex gland transplantation.

Voronoff in 1923 was the first to use chimpanzee and baboon organs for treating patients. The success described in this case quickly resulted in the procedure gathering interest. But that times none of surgeons used microsurgery to join blood vessels of the graft to the host’s circulation, resulting in ischemic necrosis preceded by organ rejection [31].

With the advent of synthetic testosterone and other steroid hormones in 1935, the clinical indications of testicular transplantation as a form of androgen therapy gradually became obsolete.

In 1978, Silber [32] published a case report claiming the first entire human testis transplant. He described the case of two genetically identical male twins, one born with two normally functioning testicles and the other born with none. Using microvascular techniques, Silber successfully transplanted a testicle from the healthy twin into the anorchic brother, and, within 2 h of the operation, normal levels of testosterone were measured in both the donor and the recipient. FSH and LH levels also gradually normalized, and, over several months, the sperm count and motility also reached normal levels in the recipient.

The problems arising from the size of the testis and its fibrous capsule led some transplanters to use sliced or minced organs. Kearns, who reimplanted testicular tissue subcutaneously in a victim of accidental castration, reported the most plausible case [33].

According to this report, testosterone was being produced by the autograft, but without the normal architecture of the seminiferous epithelium, it is hard to understand how germ cell transfer could have restored spermatogenesis. Therefore, efforts to develop tissue grafting for the purpose of improving testosterone levels in hypogonadal men are more likely to succeed than are attempts at restoring fertility. The former goal appears to be simple, requiring the transfer of interstitial cells (Leydig cells), which are readily isolated from the donor testes by means of collagenase. Interstitial cells grafted in castrated rodents resulted in partial restoration of body weight, and testosterone levels above those of controls [34–36]. A number of vehicles and several implantation sites for interstitial cells have been tried, but none fully replaced testicular androgen production.

However, in 2009, Sun reported the successful restoration of androgen production in prepubertal rats undergoing Leydig cell transplantation. Serum testosterone levels were reported as normal 12 weeks post-transplantation with a high rate of survival and functionality of transplanted cells [37].

In the twenty-first century, attention turned to testicular transplantation mainly as a therapeutic intervention for infertility. This scenario arises in oncology patients who face courses of chemotherapy that jeopardize their fertility. Cryopreservation of sperm leaves these patients with a finite resource of fertility and is associated with only modest rates of successful future conception. Cryopreservation is also not a suitable option for prepubertal patients who have not yet started to produce sperm [38].