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The loss of glucocorticoid receptor accelerates ovarian ageing in zebrafish

ABSTRACT: Ovarian aging and reproductive decline are key indicators of mid-life aging in females, with stress and elevated glucocorticoids (GCs) being significant contributors to the acceleration of this process. GCs act through both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). While previous studies have shown that the ubiquitous knockout of GR leads to accelerated ovarian aging in zebrafish, the underlying mechanisms remain poorly understood. This study aimed to investigate the effects of GR loss on reproductive aging by performing RNA-seq to analyze transcriptional changes in the ovaries of adult GR knockout (GRKO) zebrafish. Our findings reveal that GRKO ovaries exhibit a high frequency of typical follicular atresia (TFA), with increased cellular proliferation at 6 months of age. Pathways involved in mitochondrial dysfunction were also upregulated in 6-month-old GRKO ovaries, suggesting that mitochondrial dysfunction and increased reactive oxygen species (ROS) contribute to the accelerated aging observed in GRKO zebrafish. These results indicate that the loss of GR alters key cellular, immune, and metabolic processes, driving accelerated ovarian aging in zebrafish.

ORGANISM(S): Danio rerio

PROVIDER: GSE305261 | GEO | 2026/08/11

REPOSITORIES: GEO

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