FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

Transplantation of testicular tissues and cells has been proposed as a future clinical option for patients who have had testicular tissue cryopreserved prior to receiving gonadotoxic therapies. Whilst this approach remains experimental, success using animal models and successful transplantation of ovarian tissue resulting in live births in female patients provides optimism for the development of clinical applications involving transplantation of testicular tissue in males. Careful consideration must be given to patient groups that may benefit from this approach in the future. Current research is focused on optimising patient selection, methods for tissue cryopreservation and development of transplantation techniques that might restore sperm production or future fertility in males. Crucially, attention must be focused on ensuring safety of transplantation, including eliminating the potential for infection or re-introducing malignancy. Furthermore the genetic/epigenetic integrity of any gametes generated must be ensured to allow generation of normal offspring. This review will provide an overview of the current status of transplantation of testicular tissue and cells for fertility preservation in males.

Orthotopic testicular transplantation in mice

A method of revascularized orthotopic testicular transplantation (OTT) was developed in mice. The left testis was selected as donor graft for the operation due to less variation in anatomy. There were three groups: 1) a control group (n=24), 2) a group of castrated mice (n=24), and 3) a group in which OTT (n=24) was performed. Morphologically, the transplanted testes showed active spermatogenesis and normal structure of epididymis at 4 and 5 weeks. The function of the transplants was examined by RIA at designed time points. LH, FSH, and testosterone showed return to normal levels at 4 weeks. To our knowledge, this is the first report of successful revascularized OTT in mice. The model may prove useful in research in reproductive medicine, especially using knockout and transgenic mice.

Spermatogenesis following syngeneic testicular transplantation in Balb/c mice

Transplantation of spermatogonial stem cells in cross-species has been widely used to study the function of Sertoli cells and the effect of phylogenetic distance between donor and recipient animals on the outcome of spermatogonial transplantation, whereas there have been only a few reports on the transplantation of testis tissue. The objective of the present study was to examine the development of grafted testes and the kinetics of spermatogenesis following syngeneic testicular transplantation in both male and female recipient Balb/c mice in an effort to establish an in vivo culture system and to compare the effects of host sex on spermatogenesis. The testes from 5-day-old Balb/c mice were transplanted under the dorsal skin of four-week-old mice. Twenty male and twenty female Balb/c mice were used as the hosts and each host received 4 grafts. The recipient mice were killed at 1, 2, 3, 5, 7, 9, 12 and 15 weeks after transplantation. The graft survival rate and graft size were measured. The status of spermatogenesis was assessed by histological analyses. The expression of the spermatid-specific Protamine-2 gene was examined by RT-PCR. Overall, 70.3% of the testicular grafts in male hosts and 67.2% in female hosts survived. All recovered grafts had increased in volume, some of them had increased by more than 30-fold. The architecture of the seminiferous tubules in female hosts appeared to be better than that in male hosts. The round spermatids were the most advanced germ cells until 15 weeks after transplantation, and no complete spermatozoon was observed in any of the grafts. The expression of protamine-2 was detected in grafts from 5 weeks posttransplantation in both male and female hosts, confirming that the spermatogenic cells differentiated into spermatids. In contrast to grafts, the testes of male hosts had a normal histological appearance. The results showed the schedule of spermatogenesis following syngeneic testicular transplantation in both male and female hosts. This model could be useful for further studies involving the endocrinology of the testis and the mechanisms of spermatogenesis.

The results of testicular transplantation in brown leghorn hens

The grafting of reproductive tissue in various abnormal environments— auto-, homo-, or heteroplastically—has proved a useful method of approach to the question of the functions and activities of the sex-gland. It has also opened up a phase of this problem which could not be readily examined otherwise—that of the much debated points of the possibility of successful transplantation of reproductive tissue into an individual of the opposite sex, and of the consequence of such transplantation both on the gonads themselves and on their associated sex characters. Work along these lines has been confined chiefly to mammals. In recent years extensive experiments have been carried out by Steinach, Sand, Lip-schütz and Moore. In birds Sand, Pezard, and Zawadowsky have been able to obtain artificial hermaphrodites, but only in isolated cases. The present report concerns a preliminary series of experiments in the fowl, in which testes grafts were implanted into females.