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BOR - Papers in Press, published online ahead of print April 2, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.016519
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BIOLOGY OF REPRODUCTION 69, 412–420 (2003)
DOI: 10.1095/biolreprod.103.016519
© 2003 by the Society for the Study of Reproduction, Inc.

Testis

Restoration of Fertility by Germ Cell Transplantation Requires Effective Recipient Preparation1

Clayton J. Brinster, Buom-Yong Ryu, Mary R. Avarbock, Levent Karagenc, Ralph L. Brinster, and Kyle E. Orwig2

Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Spermatogonial transplantation provides access to the mammalian germline and has been used in experimental animal models to study stem cell/niche biology and germline development, to restore fertility, and to produce transgenic models. The potential to manipulate and/or transplant the germline has numerous practical applications that transcend species boundaries. To make the transplantation technology more broadly accessible, it is necessary to develop practical recipient preparation protocols. In the current study, mouse recipients for spermatogonial transplantation were prepared by treating pregnant females with the chemotherapeutic agent busulfan at different times during gestation. Donor germ cells were introduced into the testes of male progeny between 5 and 12 days postpartum. Analysis of recipient animals revealed that busulfan treatment of pregnant females on 12.5 days postcoitum was the most effective; male progeny transplanted with donor germ cells became fertile and passed the donor genotype to 25% of progeny. This approach was effective because 1) the cytoablative treatment reduced (but did not abolish) endogenous spermatogenesis, creating space for colonization by donor stem cells, 2) residual endogenous germ cells contributed to a healthy testicular environment that supported robust donor and recipient spermatogenesis, and 3) fetal busulfan-treated males could be transplanted as pups, which have been established as better recipients than adults. Laboratory mice provide a valuable experimental model for developing the technology that now can be applied and evaluated in other species.

1 Histological sections were produced in the University of Pennsylvania Institute for Human Gene Therapy Morphology Core (grant 5-P30-DK-47747-07). Financial support for the research was from the National Institutes of Child Health and Human Development Grant 36504, the Commonwealth and General Assembly of Pennsylvania, and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.

2 Correspondence: K.E. Orwig, Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3850 Baltimore Ave., Philadelphia, PA 19104. FAX: 215 898 0667; korwig{at}vet.upenn.edu






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Copyright © 2003 by the Society for the Study of Reproduction.