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PMID: 16456131 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Effects of aging and niche microenvironment on spermatogonial stem cell self-renewal.

Stem cells (Dayton, Ohio) ·Vol. 24 ·No. 6 ·2006-06-00 ·Pages 1505-11

Ryu BY, Orwig KE, Oatley JM, Avarbock MR, Brinster RL

Abstract

Aging is evident in most tissues and organ systems, but the mechanisms of aging are difficult to identify and poorly understood. Here, we test the hypothesis that aging results in uncorrected defects in stem cell and/or niche function, which lead to system failure. We used the spermatogonial stem cell (SSC) transplantation assay to determine the effect of aging on testis stem cell/niche function in mice. Between 12 and 24 months of age, male mice experienced a declining level of fertility associated with decreased testis weight, level of spermatogenesis, and total stem cell content. However, when stem cells were consecutively passaged at 3-month intervals to testes of young males, these stem cells continued to produce spermatogenesis for more than 3 years. Thus, SSC self-renewal continues long past the normal life span of the animal when the stem cell is continually maintained in a young niche/microenvironment. Moreover, these data suggest that infertility in old males results from deterioration of the SSC niche and failure to support an appropriate balance between stem cell self-renewal and differentiation.

MeSH Terms
Aging/genetics,pathology Animals Cell Differentiation Gene Expression Glial Cell Line-Derived Neurotrophic Factor/genetics Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics Infertility, Male/etiology,pathology Male Mice Mice, Inbred C57BL Mice, Transgenic Spermatogenesis Spermatogonia/cytology,metabolism,transplantation Stem Cell Transplantation Stem Cells/cytology,metabolism Testis/cytology,metabolism
Chemicals
Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor Receptors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ryu Buom-Yong
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
Orwig Kyle E
Oatley Jon M
Avarbock Mary R
Brinster Ralph L
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Article Info
Journal
Stem cells (Dayton, Ohio)
Abbr.
Stem Cells
ISSN
1066-5099
DOI
10.1634/stemcells.2005-0580
Published
2006-06-00
Epub
2006-00-02
Pages
1505-11
Language
English
Region
United States
NLM ID
9304532
PMCID
PMC5501308
Subset
IM
Grants
NICHD NIH HHS · R01 HD044445 · United States
NIA NIH HHS · AG 024992 · United States
NICHD NIH HHS · HD 044445 · United States
External Links
PubMed source DOI: 10.1634/stemcells.2005-0580 PMC Full Text View journal details
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