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BOR - Papers in Press, published online ahead of print April 16, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.016352
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BIOLOGY OF REPRODUCTION 69, 701–707 (2003)
DOI: 10.1095/biolreprod.103.016352
© 2003 by the Society for the Study of Reproduction, Inc.


Testis

Homing Efficiency and Proliferation Kinetics of Male Germ Line Stem Cells Following Transplantation in Mice1

Makoto C. Nagano2

Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada H3A 1A1

Stem cells in the male germ line (spermatogonial stem cells [SSCs]) are an important target for male fertility restoration and germ line gene modification. To establish a model system to study the biology and the applications of SSCs in mice, I used a sequential transplantation strategy to analyze the process by which SSCs colonize the stem cell niche after transplantation and to determine the efficiency of the process (homing efficiency). I further analyzed the proliferation kinetics of SSCs after colonization. The number of SSCs gradually decreased during the homing process, and only 12% of SSCs successfully colonized the niche on Day 7 after transplantation, but the number of SSCs increased by Day 14. Thus, homing efficiency of adult mouse SSCs is 12%. These results indicate that SSCs are rapidly lost upon transplantation and require ~1 wk to settle into their niches before initiating expansion. Using this SSC homing efficiency, I calculated that ~3000 SSCs exist in one normal adult testis, representing ~0.01% of total testis cells. Between 7 days and 1 mo after transplantation, SSCs proliferated 7.5-fold. However, they did not significantly proliferate thereafter until 2 mo, and only 8 SSCs supported one colony of donor-derived spermatogenesis from 1 to 2 mo. These results suggest that self-renewal and differentiation of SSCs are strictly regulated in coordination with the progress of an entire unit of regenerating spermatogenesis.

1 This research was supported by the Canadian Institutes of Health Research (MOP-49444). The author is a recipient of the RVH/MGH award.

2 Correspondence: Makoto C. Nagano, Royal Victoria Hospital, Room F3.07, 687 Pine Ave. West, Montreal, PQ H3A 1A1, Canada. FAX: 514 843 1662; makoto.nagano{at}muhc.mcgill.ca







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