Homologous testis transplantation in dogs.

There is growing interest in the possible use of homologous testis transplantation for the treatment of anorchia and male infertility. In order to test the surgical and immunological feasibility of this therapy, three series of experimental studies of homologous testis transplantation were carried out in dogs. In the first pilot study, four beagles from the same litter were transplanted using microsurgical techniques for end-to-end anastomosis of the testicular vessels and the vas deferens. These dogs received cyclosporin A (CyA) for 3 months after transplantation. The longest functional graft survival in this series was 163 days, strongly suggesting that long-term survival of a homologously transplanted testis graft is possible. A second series of operations was performed on ten mongrel dogs. The same surgical technique was employed and the series was divided into three groups. Group 1 received CyA monotherapy, group 2 a combination of CyA and prednisolone, and group 3 received no immunosuppression. The average graft survival time in this series was 28 days, significantly less than the 71 days in the first series. The dogs in group 2, however, had graft survival times that were three times longer than those in the other two groups, suggesting that CyA in combination with prednisolone yields the best graft survival. In the third series, five littermates received a testis graft after castration. Immunosuppression was achieved by administration of CyA and prednisolone for 3 months. In three out of five animals, the graft survived until the immunosuppressive therapy was suspended. Histological biopsies of the graft 3 months after transplantation showed the same maturation of sperm cells as in the control testis of the same dog. The results of the last series suggest that long-term survival of homologously transplanted testis grafts in dogs is, indeed, possible with the aid of CyA and prednisolone.

Transplantation of the testis; from the past to the present.

Since the development of surgery, the possibility of testis transplantation has fascinated man for centuries. Hunter and Berthold are considered to be the most important investigators in this field and, in addition, to be the founders of modern endocrinology. The association of testis transplantation with rejuvenation led to widespread popularity for this treatment in the first three decades of the twentieth century. At the same time, controversies concerning the aim of the treatment have coloured the early years of endocrinology. In the 1960s renewed interest in the subject arose for experimental reasons, leading to the development of microsurgical techniques for autotransplantation of high-lying undescended testes in children. Homologous testis transplantation has never become a subject of great interest, probably for ethical reasons. This possible treatment for hypogonadism, however, has been developed experimentally and has been performed in man only in Russia and China, evidently with success. The details of these studies and their outcomes are discussed.

Origin and biology of a testicular Wilms' tumor.

A pure triphasic testicular Wilms' tumor, without teratomatous elements, was studied using multiple techniques. Carcinoma in situ (CIS), the characteristic precursor of testicular germ cell tumors of adults (TGCTs), was found in the adjacent parenchyma. Flow cytometric analysis showed a single hypotriploid tumor stem line. Karyotyping of the tumor revealed some numerical and structural abnormalities, including an i(12p), the chromosomal marker of TGCTs. In situ hybridization supported the karyotypic findings, and showed a similar numerical distribution in CIS and the tumor. Molecular analysis of the tumor illustrated that all short arms of chromosome 12, including i(12p), were of maternal origin. No 12q deletions were detected. In spite of complete loss of the paternal 11p13 band, the zinc finger regions and exons 2 and 6 of the WT1 gene contained no aberrations. Therefore, this tumor suppressor gene is not inactivated due to aberrations in the studied regions. In addition, all four WT1 alternative transcripts were expressed in the tumor. No aberrations were found in chromosomal bands 11p15.5, 16q22.1, and 16q24. Both parental alleles of the human imprinted genes H19 and IGF2 were expressed in the tumor. This is the first report on the chromosomal and molecular characterization of an extrarenal Wilms' tumor. Its germ cell origin was unequivocally demonstrated.