The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions.

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% O₂. Through the generation of a germline-specific Epas1 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 met

SUBMITTER: Bernstein IR 

PROVIDER: S-EPMC10700845 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature