Astaxanthin supplementation influences mitophagy and mitochondrial biogenesis in granulosa cells of women with polycystic ovary syndrome undergoing assisted reproductive treatment

Polycystic ovary syndrome (PCOS) is a common endocrine disorder and a major cause of anovulatory infertility, in which mitochondrial dysfunction, impaired mitochondrial biogenesis, and oxidative stress contribute to follicular atresia. Astaxanthin (AST), a potent antioxidant, may modulate oxidative balance and mitochondrial pathways. This triple-blind, placebo-controlled randomized trial evaluated the effects of AST on mitophagy and mitochondrial biogenesis in granulosa cells of women with PCOS. Sixty women with PCOS were randomly assigned to receive AST or placebo for 6 weeks. Gene expression of PGC-1α, TFAM, BAX, and BCL2, protein levels of PINK1, Parkin, and SIRT1, antioxidant status (TAC, MDA), and mitochondrial ultrastructure were assessed. AST supplementation significantly increased TAC levels, whereas MDA showed no significant change. At the transcriptional level, TFAM and BCL2 were significantly upregulated, whereas BAX was downregulated, while PGC-1α expression tended to increase without reaching statistical significance. No significant differences were observed in PINK1, Parkin, or SIRT1 protein levels between groups. Ultrastructural analysis suggested better preservation of mitochondrial membrane integrity in the AST group. The number of MII oocytes was significantly higher following AST supplementation, alyhough no significant differences were observed in embryo number or quality. However, these findings should be interpreted with caution, as this study may not have been powered to detect definitive effects on downstream reproductive outcomes such as fertilization and embryo quality. Further large-scale trials are required to confirm these results and clarify the clinical relevance of AST supplementation in PCOS patients.