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Transplantation of male germ line stem cells restores fertility in infertile mice

Nature Medicine volume 6, pages 29–34 (2000)Cite this article

Abstract

Azoospermia or oligozoospermia due to disruption of spermatogenesis are common causes of human male infertility. We used the technique of spermatogonial transplantation in two infertile mouse strains, Steel (Sl) and dominant white spotting (W), to determine if stem cells from an infertile male were capable of generating spermatogenesis. Transplantation of germ cells from infertile Sl/Sld mutant male mice to infertile W/Wv or Wv/W54 mutant male mice restored fertility to the recipient mice. Thus, transplantation of spermatogonial stem cells from an infertile donor to a permissive testicular environment can restore fertility and result in progeny with the genetic makeup of the infertile donor male.

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Figure 1: Steel factor (Kit ligand)–Kit receptor interaction in the mouse testis, with phenotypes and testis sizes of mice.
Figure 2: Microscopic appearance of seminiferous tubules of W/Wv recipient mouse testes after transplantation of Sl/ Sld germ cells.
Figure 3: Pedigree and Southern blot analysis of seven weanling mice from the mating of a white (open symbol) W/Wv recipient male mouse (number 1803) to a black (filled symbols) wild-type (+/+, C57BL/6) female mouse.

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Acknowledgements

We thank M. Nagano, K. Orwig and T. Shinohara for discussions and suggestions. We also thank O. Jacenko and M. Campbell for advice and assistance with DNA analysis, and J. Barker for the W54 mouse line. In addition, we thank C. Freeman and R. Naroznowski for assistance with animal maintenance and experimentation, and J. Hayden (registered biological photographer; Blue Bell, Pennsylvania., BioGraphics) for photography and Fig. 1 schematic. Supported by the National Institutes of Health (NICHD 36504), the US Department of Agriculture/National Research Institute Competitive Grants Program (99-35205-8620), the Commonwealth and General Assembly of Pennsylvania, and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.

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Author notes

  1. Takehiko Ogawa

    Present address: Department of Urology, School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

  2. Ina Dobrinski

    Present address: Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, 382 W. Street Rd., Kennett Square, 19348, Pennsylvania, USA

Authors and Affiliations

  1. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3850 Baltimore Ave., Philadelphia, 19104, Pennsylvania, USA

    Takehiko Ogawa, Ina Dobrinski, Mary R. Avarbock & Ralph L. Brinster

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Ogawa, T., Dobrinski, I., Avarbock, M. et al. Transplantation of male germ line stem cells restores fertility in infertile mice. Nat Med 6, 29–34 (2000). https://doi.org/10.1038/71496

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