Adult human testicular tissue with impaired spermatogenesis survives as ectopic xenograft

Abstract

To provide a laboratory model to evaluate survival and maintenance of adult human spermatogenesis from men with a variety of pathological conditions. Research study (IRB-approved) of transplantation by xenografting of human testicular biopsies in immunodeficient mice. A total of 8 testicular biopsies, obtained from four men diagnosed with obstructive azoospermia and one man with maturation arrest, and multiple testicular samples from two testes (orchiectomy specimen) of a patient undergoing a sex reversal operation after prolonged hormonal suppression, were used for the experiments. The specimens were grafted into castrated, six-week old male, immunodeficient ICR SCID mice. At the time of grafting a piece of testicular tissue was also fixed for histological exam and to serve as a reference for graft development. The remaining fragments of testis tissue were inserted subcutaneously into the dorsal skin and analyzed at different time intervals (between 1 and 19 weeks). At the time of analysis, the following were documented: a) histology; b) measurement of the diameter of the seminiferous tubules; c) maintenance or development of spermatogenesis. The xenografts from each donor survived and all established blood supply; however, grafts from donors with complete spermatogenesis at the time of grafting showed consistently massive degenerative changes of the germinal epithelium and progressive decline and disappearance of spermatogenic activity. On the other hand, from 2 and up to 19 weeks, all the testis grafts of patients exhibiting absent spermatogenesis maintained their tubular morphology and showed almost no degenerative changes. These pioneering observations suggest that: a) adult human testis grafts from patients with complete spermatogenesis undergo progressive degenerative changes in xenografts; b) testis grafts of patients with less advanced spermatogenesis (histologically comparable to prepubertal boys) are more likely to survive. These findings provide strong support to the hypothesis that, as already demonstrated in domestic animal species, xenografting could be used to initiate and maintain spermatogenesis in grafts obtained from prepubertal boys prior to gonadotoxic treatments.