AI Article Synopsis
- This study investigates how low oxygen levels (hypoxia) and the protein EPAS1 affect spermatogonial stem cell (SSC) function in mouse testes.
- The researchers found that SSCs thrive in low-oxygen environments and need EPAS1 for proper functionality, especially after stressful situations like chemotherapy.
- The results could lead to better treatment methods for male infertility, particularly in young cancer survivors, by improving how SSCs are cultured.
Article Abstract
In this study we explored the role of hypoxia and the hypoxia-inducible transcription factor EPAS1 in regulating spermatogonial stem cell (SSC) function in the mouse testis. We have demonstrated that SSCs reside in hypoxic microenvironments in the testis through utilization of the oxygen-sensing probe pimonidazole, and by confirming the stable presence of EPAS1, which is degraded at >5% O. Through the generation of a germline-specific knockout mouse line, and through modulation of EPAS1 levels in primary cultures of spermatogonia with the small drug molecule Daprodustat, we have demonstrated that EPAS1 is required for robust SSC function in regenerative conditions (post-transplantation and post-chemotherapy), via the regulation of key cellular processes such as metabolism. These findings shed light on the relationship between hypoxia and male fertility and will potentially facilitate optimization of culture conditions for infertility treatment pipelines using SSCs, such as those directed at pediatric cancer survivors.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700845 | PMC |
| http://dx.doi.org/10.1016/j.isci.2023.108424 | DOI Listing |
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