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Aging of Male Germ Line Stem Cells in Mice¹

Departments of Obstetrics and Gynecology³ and of Pharmacology and Therapeutics,⁴ McGill University, Montreal, Quebec, Canada H3A 1A1

ABSTRACT

In the present study, we investigated the effect of aging on spermatogonial stem cells (SSCs) and on the testicular somatic environment in ROSA26 mice. First, we examined testis weights at 2 mo, 6 mo, 1 yr, and 2 yr of age. At 1 and 2 yr, bilateral atrophied testes were observed in 50% and 75% of the mice, respectively; the rest of the mice had testis weights similar to those of young mice. Next, we evaluated the number and the activity of aged SSCs using spermatogonial transplantation. Numbers of SSCs in atrophied testes decreased in an age-dependent manner to as low as 1/60 of those in testes of young mice. Numbers of SSCs in nonregressed testes were similar regardless of age. The colony length, which is indicative of the potential of SSCs to regenerate spermatogenesis, was similar with donor cells from atrophied testes of 1-yr-old mice and those from testes of young mice, suggesting that SSCs remaining in 1-yr atrophied testes were functionally intact. Colonies arising from SSCs derived from 2-yr atrophied testes were significantly shorter, however, indicating that both SSC numbers and activity declined with age. Finally, we transplanted donor cells from young animals into 1- and 2-yr atrophied testes. Although the weight of 2-yr testes did not change after transplantation, that of 1-yr testes increased significantly, indicating that 1-yr, but not 2-yr, atrophied testes are permissive for regeneration of spermatogenesis by SSCs from young mouse testes. These results demonstrate that both SSCs and somatic environment in the testis are involved in the aging process.

aging, spermatogenesis, testis

¹ Supported by the Canadian Institutes of Health Research (MOP-49444 to M.N. and MOP-57882 to B.R. and M.N.) and the Canadian Foundation for Innovation (4177 to M.N.). K.T.E. is supported by The Stem Cell Network. M.N. is a Fondation pour la Recherche en Sante du Quebec scholar.

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

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