Effects of Aging and Niche Microenvironment on Spermatogonial Stem Cell Self-Renewal
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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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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.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [154]
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Self-citation
- 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
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-02-02
- Volume
- 24
- Issue
- 6
- Pages
- 1505-1511
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- PMC
- PMC5501308
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- 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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