Astaxanthin activates PI3K/AKT and AMPK signaling to alleviate oxidative stress and improve mouse oocyte In vitro maturation.

Abstract

Assisted reproductive technology (ART) has broad applications in livestock production, biomedical research, and developmental biology. Oocyte in vitro maturation (IVM) is a critical step in ART; however, oxidative stress-induced impairment of oocyte quality remains a major obstacle limiting its efficiency and broader application. Supplementation of antioxidants in IVM medium is an effective strategy to alleviate oxidative stress. Astaxanthin, a potent natural antioxidant, has shown protective potential in reproductive biology, but its specific mechanism of action during oocyte maturation remains unclear. In this study, we investigated the effects of astaxanthin on mouse oocyte IVM and explored the underlying molecular mechanisms. Treatment of germinal vesicle-stage oocytes with 9 μg/mL astaxanthin significantly improved the in vitro maturation rate, reduced oxidative stress, and enhanced mitochondrial activity. Notably, transcriptomic analysis combined with pharmacological rescue experiments revealed that astaxanthin alleviated oxidative stress, protected mitochondrial function, and inhibited apoptosis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) signaling pathways, thereby significantly improving the quality of mouse oocytes during IVM. These findings reveal a dual-pathway regulatory mechanism through which astaxanthin improves oocyte quality and provide a potential strategy for optimizing IVM culture systems, assisted reproduction, and livestock embryo production.