ArticleStem cells (Dayton, Ohio)2012
The in vivo response of stem and other undifferentiated spermatogonia to the reversible inhibition of glial cell line-derived neurotrophic factor signaling in the adult.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Unraveling the effect of the inflammatory microenvironment in spermatogenesis progression.Cell and tissue research · 2023Article
- Low nephron endowment increases susceptibility to renal stress and chronic kidney disease.JCI insight · 2023Article
- Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?Frontiers in endocrinology · 2022Article
- The Regulation of Spermatogonial Stem Cells in an Adult Testis by Glial Cell Line-Derived Neurotrophic Factor.Frontiers in endocrinology · 2022Review
- Spermatogonial Stem Cell Numbers Are Reduced by Transient Inhibition of GDNF Signaling but Restored by Self-Renewing Replication when Signaling Resumes.Stem cell reports · 2021Article
- Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules.Scientific reports · 2021Article
- FSH regulates RA signaling to commit spermatogonia into differentiation pathway and meiosis.Reproductive biology and endocrinology : RB&E · 2021Review
- CARF promotes spermatogonial self-renewal and proliferation through Wnt signaling pathway.Cell discovery · 2020Article
- CDK2 kinase activity is a regulator of male germ cell fate.Development (Cambridge, England) · 2019Article
- Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network.Stem cells (Dayton, Ohio) · 2017Article
- The production of glial cell line-derived neurotrophic factor by human sertoli cells is substantially reduced in sertoli cell-only testes.Human reproduction (Oxford, England) · 2017Article
- TSPAN8 Expression Distinguishes Spermatogonial Stem Cells in the Prepubertal Mouse Testis.Biology of reproduction · 2016Article
- Spermatogenesis: The Commitment to Meiosis.Physiological reviews · 2016Review
- Peritubular myoid cells participate in male mouse spermatogonial stem cell maintenance.Endocrinology · 2014Article
- Responses to glial cell line-derived neurotrophic factor change in mice as spermatogonial stem cells form progenitor spermatogonia which replicate and give rise to more differentiated progeny.Biology of reproduction · 2014Article
- Article
- Structure-guided inhibitor design expands the scope of analog-sensitive kinase technology.ACS chemical biology · 2013Article
- Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection.American journal of human genetics · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Maintaining adequate numbers of spermatogonial stem cells is required for the production of the millions of sperm required for male fertility. To date, however, the mechanisms that regulate the size of this pool in the adult are poorly defined. Glial cell line-derived neurotrophic factor (GDNF) is required for establishing this pool in the prepubertal animal, but its in vivo function in the normal adult testis has never been examined directly. We used a chemical-genetic approach to address this issue. We generated mice carrying a single amino acid mutation (V805A) in Ret, the kinase subunit of the GDNF receptor. This mutation does not affect normal GDNF signaling but renders it susceptible to inhibition by the ATP competitive inhibitor, NA-PP1. When GDNF signaling was blocked in adults for 11 days, only a few cells remained that expressed the stem spermatogonial markers, Gfrα1 and Zbtb16, and testicular Ret mRNA content was reduced markedly. These decreases were associated with depletion of functional stem spermatogonia; some were lost when GDNF signaling was inhibited for only 2 days while others survived for up to 11 days. However, when signaling was restored, the remaining stem cells proliferated, initiating tissue restoration. In conclusion, these results provide the first direct proof that GDNF acutely regulates the number of spermatogonial stem cells in the normal adult testis. Additionally, these results demonstrate different sensitivities among subpopulation of these stem cells to inhibition of GDNF signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.