Cited by 266Sperm and Testicular FunctionReproductive Biology and FertilityAnimal Genetics and Reproduction

Effects of Aging and Niche Microenvironment on Spermatogonial Stem Cell Self-Renewal

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Ryu, Buom-Yong, Orwig, Kyle E., Oatley, Jon M., Avarbock, Mary R., Brinster, Ralph L.·2006·Stem Cells

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.

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Crossref · 10.1634/stemcells.2005-0580

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  • In Sertoli cells, glial cell-derived neurotrophic factor-needed to regulate spermatogonial stem cell self-renewal and differentiation-drops sharply with age.

    “Similarly, expression of glial cell–derived neurotrophic factor, which is required for normal regulation of spermatogonial stem cell self-renewal and differentiation, is markedly reduced with age in Sertoli cells, the nurse cells of the testes154.”

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Authors
Ryu, B.-Y., Orwig, K. E., Oatley, J. M., Avarbock, M. R., & Brinster, R. L.
Affiliations
University of Pennsylvania (US)
Corresponding author
Brinster, Ralph L.
Venue
Stem Cells
Published
2006-02-02
Volume
24
Issue
6
Pages
1505-1511
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
OpenAlex
W1971100182
Cited by
265
References
31
Citations by year
2026: 2 · 2025: 11 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 13 · 2020: 16 · 2019: 19 · 2018: 13 · 2017: 10 · 2016: 13 · 2015: 17 · 2014: 18 · 2013: 12 · 2012: 22
FWCI
18.65
Type
journal article
Language
en
Open access
Locations
  • Stem Cells (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG024992, AG024992)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD044445, R01HD044445)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Keywords
aging, spermatogonial stem cells, stem cell self-renewal, stem cell niche, microenvironment, male infertility, spermatogenesis, testis, stem cell transplantation, stem cell differentiation, fertility decline
MeSH terms
Aging, Animals, Cell Differentiation, Infertility, Male, Male, Mice, Inbred C57BL, Mice, Transgenic, Spermatogenesis, Spermatogonia, Stem Cells, Testis, Gene Expression, Stem Cell Transplantation, Glial Cell Line-Derived Neurotrophic Factor Receptors, Glial Cell Line-Derived Neurotrophic Factor, Mice

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