Astaxanthin attenuates CTX-induced premature ovarian failure by alleviating ovarian apoptosis and autophagy in vivo.

BACKGROUND

Cyclophosphamide (CTX) is a commonly used chemotherapeutic agent for breast cancer that frequently causes premature ovarian failure (POF), a clinical syndrome characterized by menstrual irregularities in women under the age of 40 years, accompanied by elevated serum follicle-stimulating hormone (FSH) and decreased estrogen levels. Astaxanthin (AS), a natural antioxidant, has been shown to exert various biological effects, including anti-aging and anti-inflammatory effects. However, further investigation into its anti-ovarian aging mechanism is warranted.

METHODS

Two-month-old female mice and CTX-induced POF model mice were used. Hematoxylin and eosin staining, immunohistochemical staining, TUNEL assays, Western blotting, and qPCR analyses were employed to evaluate ovarian function and related phenotypes after astaxanthin treatment. Subsequently, network pharmacology analysis was used to elucidated potential targets.

RESULTS

Astaxanthin intervention significantly ameliorated estrous cycle disorder in POF mice and restored serum levels of anti-Müllerian hormone (AMH) and estradiol (E2). Meanwhile, astaxanthin markedly enhanced the ovarian reserve and suppressed CTX-induced apoptosis and autophagy. Mechanistically, astaxanthin was found to modulate the CYP19A1 expression, thereby enhancing ovarian function.

CONCLUSION

This study elucidates the mechanism by which astaxanthin improves ovarian function through the CYP19A1, providing potential molecular targets and therapeutic strategies for the clinical treatment of POF.