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BOR - Papers in Press, published online ahead of print October 30, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.009977
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BIOLOGY OF REPRODUCTION 68, 1064–1071 (2003)
DOI: 10.1095/biolreprod.102.009977
© 2003 by the Society for the Study of Reproduction, Inc.


Testis

Restoration of Spermatogenesis in Infertile Mice by Sertoli Cell Transplantation1

Takashi Shinohara3,a, Kyle E. Orwiga, Mary R. Avarbocka, and Ralph L. Brinster2,a

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

The niche is considered to play an important role in stem cell biology. Sertoli cells are the only somatic cells in the seminiferous tubule that closely interact with germ cells to create a favorable environment for spermatogenesis. However, little is known about how Sertoli cells develop to form the male germ line niche. We report here that Sertoli cells recovered and dissociated from testes of donor male mice can be microinjected into recipient testes, form mature seminiferous tubule structures, and support spermatogenesis. Sertoli cells from perinatal donors had a dramatically greater capacity for generating seminiferous tubules than those from adult donors. Furthermore, transplantation of wild-type Sertoli cells into infertile Steel/Steeldickie testes created a permissive testicular microenvironment for generating spermatogenesis and spermatozoa. Thus, our results demonstrate that the male germ line stem cell niche can be transferred between animals. In addition, the technique provides a novel tool with which to analyze spermatogenesis and might provide a mechanism for correcting fertility in males suffering from supporting cell defects.

1 T.S. was supported by the Japan Society for Promotion of Science. 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 Institute 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 Corespondence: R.L. Brinster, School of Veterinary Medicine, University of Pennsylvania, 3850 Baltimore Avenue, Philadelphia, PA 19104. FAX: 215 898 0667

3 Current address: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, Japan 606-8501




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