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Hum. Reprod. Advance Access published online on May 26, 2005
Human Reproduction, doi:10.1093/humrep/dei096
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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@oupjournals.org
Received March 23, 2005
Revised April 25, 2005
Accepted April 27, 2005

Article

Germline niche transplantation restores fertility in infertile mice

M. Kanatsu-Shinohara 1, H. Miki 2, K. Inoue 2, N. Ogonuki 2, S. Toyokuni 3, A. Ogura 2, and T. Shinohara 4*

1 Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 Japan and Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
2 The Institute of Physical and Chemical Research (RIKEN), Bioresource Center, Ibaraki 305-0074, Japan
3 Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
4 Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan

* To whom correspondence should be addressed.
T. Shinohara, E-mail: tshinoha{at}virus.kyoto-u.ac.jp


  Abstract

BACKGROUND: Stem cells interact closely with their microenvironment or niche, and abnormalities in niche compromise the self-renewing tissue. In testis, for example, Sertoli cells interact with germ cells, and defects in Sertoli cells compromises spermatogenesis, leading to male infertility. However, it has not been possible to restore spermatogenesis from endogenous stem cells in infertile testis with environmental defects METHODS AND RESULTS: When healthy Sertoli cells from infertile white spotting (W) mouse were transplanted into the seminiferous tubules of infertile Steel (Sl) mouse testis that had defective Sertoli cells, spermatogenesis occurred from Sl stem cells in the recipient testis. On average, 1.1% of the recipient tubules showed spermatogenesis. Furthermore, in a microinsemination experiment with germ cells that developed in the testis, we obtained four normal offspring from 114 successfully injected oocytes. CONCLUSIONS: This study demonstrates that defects in male germline microenvironment can be corrected by Sertoli cell transplantation. Although further improvements are required to enhance the low efficiency of spermatogenesis, the ability to correct environmental defect by niche transplantation has important implications in developing new strategies for treating incurable disorders in self-renewing tissues.

Keywords: infertility; niche; Sertoli cells; spermatogenesis; transplantation.
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