Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation

• Published in: Human reproduction (Oxford) 2010-05, Vol.25 (5), p.1113-1122
• Main Authors: Sato, Y., Nozawa, S., Yoshiike, M., Arai, M., Sasaki, C., Iwamoto, T.
• Format: Article
• Language: English
• Subjects: Animals; cdc25 Phosphatases - metabolism; Cell Differentiation; Fertility; Hemangioma - pathology; Hemangioma - therapy; human; Humans; Immunohistochemistry; Infant; Leydig Cells - cytology; Male; Mice; Mice, Nude; Microscopy, Electron, Transmission; RNA-Binding Proteins - metabolism; Sertoli Cells - cytology; Spermatocytes - cytology; Spermatogenesis; Spermatogonia - cytology; Testicular Neoplasms - pathology; Testicular Neoplasms - therapy; testis; Testis - cytology; Testis - growth & development; Testis - metabolism; Testis - transplantation; Transplantation, Heterologous; xenograft
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deq001

BACKGROUND Grafting of testicular tissue into immunodeficient mice has been used to differentiate the neonatal testes from different animal species up to the level of complete spermatogenesis; however, this approach has not been successful for human testicular tissue. The aim of this study was to evaluate the capacity for differentiation of infant human testicular tissue grafts. METHODS AND RESULTS Testicular tissue from a 3-month-old patient with testicular cancer was grafted into immunodeficient nude mice. At the time of grafting, A spermatogonia were the only germ cells present in the testicular tissue. B spermatogonia and first spermatocytes were observed at 7 months and 1 year after grafting, respectively. Positive immunostaining with antibodies against BOULE and CDC25A suggested that spermatocytes in the graft were not arrested but in meiosis. Furthermore, ultrastructural and immunohistochemical analyses showed that the onset of both Sertoli cell maturation and partial differentiation of Leydig cells preceded the appearance of spermatocytes. Differentiation of testicular cells was accelerated compared with in vivo development. CONCLUSIONS Spermatogenesis in the xenograft of infant human testicular tissues proceeded successfully from the stage of spermatogonial stem cells until pachytene spermatocyte formation. The differentiation of Sertoli cells and Leydig cells was reproduced in a manner similar to that in normal testicular development. Grafting of infant human testicular tissue may be a powerful tool to examine the early period of human spermatogenesis and may pave the way for fertility preservation among infant patients.