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Hum. Reprod. Advance Access published online on October 20, 2005

Human Reproduction, doi:10.1093/humrep/dei352
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 11, 2005
Revised September 12, 2005
Accepted September 20, 2005

Article

Limited survival of adult human testicular tissue as ectopic xenograft

S. Schlatt 1, A. Honaramooz 2, J. Ehmcke 1, P.J. Goebell 3, H. Rübben 3, R. Dhir 4, I. Dobrinski 5*, and P. Patrizio 6

1 Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, BST, W952, 3500 Terrace Street, Pittsburgh PA 15261, USA and Institute of Reproductive Medicine, University Münster, Domagkstr. 11, 48149 Münster, Germany
2 Center for Animal Transgenesis and Germ Cell Research, University of Pennsylvania School of Veterinary Medicine, 382 West Street Road, Kennett Square, PA 19348, USA; Present address: Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5B4
3 Department of Urology, University Essen, Hufelandstr. 55, 45122 Essen, Germany
4 GU Pathology, Health Sciences Tissue Bank, UPMC Shadyside-Presbyterian Hospital, 5230 Center Avenue, Room WG 07, Pittsburgh PA 15232, USA
5 Center for Animal Transgenesis and Germ Cell Research, University of Pennsylvania School of Veterinary Medicine, 382 West Street Road, Kennett Square, PA 19348, USA
6 Yale University Fertility Center, 150 Sargent Drive, New Haven, CT 06511, USA

* To whom correspondence should be addressed.
I. Dobrinski, E-mail: dobrinsk{at}vet.upenn.edu


   Abstract

BACKGROUND: Grafting of testicular tissue into immunodeficient mice has become an interesting and promising scientific tool for the generation of gametes and the study of testicular function. This technique might potentially be used to generate sperm from patients whose testes need to be removed or are destroyed due to therapeutic intervention or as a consequence of disease. Here we explore whether adult human testicular tissue from patients with different testicular pathologies survives as xenograft. METHODS AND RESULTS: Testis tissue from adult patients with varying degrees of spermatogenesis was grafted into two strains of immunodeficient mice (severe combined immunodeficiency, Nu/Nu). Tissue with active spermatogenesis prior to grafting largely regressed. However, testicular tissue survival was better in cases where spermatogenesis was suppressed prior to grafting and occasionally spermatogonial stem cells survived. Cases with spermatogenic disruption were not corrected by the xenografting. CONCLUSION: Superior survival of the germinal epithelium and spermatogonia when spermatogenesis was suppressed prior to grafting could provide a novel strategy for germline preservation in pre-pubertal cancer patients. This approach could also be valuable to study the early stages of human spermatogenesis.

Keywords: fertility preservation/grafting/spermatogenesis/steroidogenesis/testis.
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