Multi-omics analysis reveals the attenuation effect of C-phycocyanin on aging-induced subfertility in female mice.

Excessive inflammatory responses within the ovary are one of the main causes of subfertility in elderly women. Eliminating these responses can reverse fertility in aged individuals. Here, we demonstrate that administering 300 mg kg^-1 day^-1 C-phycocyanin (PC) to 36-week-old female mice for 45 days can reduce age-related fertility decline, resulting in an increase in litter size from 7.53 to 10.90. PC administration in aged mice enhances ovarian antioxidant enzyme levels, promotes first polar extrusion, and supports early embryonic development. Additionally, PC increases the proportion of normal spindle-chromosome complexes, normalizes mitochondrial distribution, reduces ROS levels, and decreases early apoptosis in aged mice. Notably, PC intervention mitigates age-related changes in gut microbiota composition, serum metabolite profiles, and ovarian gene expression patterns. Mechanistically, PC exerts its effects by suppressing interferon-γ expression, attenuating interferon responses, and preventing ovarian fibrosis, thereby improving reproductive function in aged female mice. Collectively, these findings highlight PC as a potential therapeutic agent to counter age-related fertility decline through targeted anti-inflammatory mechanisms.