Lycium barbarum berry extract improves female fertility against aging-related oxidative stress in the ovary

Reproductive aging in female mammals is characterized by ovarian senescence, leading to a significant fertility decline. Lycium barbarum berry, or goji berry, is a food and medicine that appears in various formulas for treating infertility in traditional Chinese medicine. We investigated the function of an aqueous extract of Lycium barbarum berry (LB extract) to improve health status, fertility, and offspring development during female aging. Aged female mice were supplemented with LB extract, and its effects on fertility, locomotor activity, and offspring development were assessed. The results demonstrated that LB extract significantly increased pregnancy and live birth rates in naturally aged female mice. It also effectively improved aged animals' locomotor activity. Moreover, LB extract promoted the growth and development of offspring delivered from the aged animals and reduced the offspring's anxiety. During aging, fertility-related hormones gradually decline. However, the decline of anti-Müllerian hormone (AMH) and estradiol (E₂) in the serum of aged mice was restored by LB extract supplementation. Immunohistochemical analysis revealed that the levels of oxidation and the inflammatory IL-6 in intra-ovarian cells were reduced by LB extract, while the antioxidant-associated proteins peroxiredoxin 4 (PRDX4) and nuclear factor erythroid 2-related factor 2 (NRF2) were increased. Bioinformatics analysis revealed a decline in egg PRDX4 expression with age across various species. This suggests that the antioxidant function protected by LB extract through PRDX4 may consistently promote fertility enhancement by improving ovarian function across different species. Importantly, LB extract did not induce significant adverse effects on aged female mice and their offspring. These findings highlight the potential of LB as a protective agent against ovarian oxidative stress, which preserves ovarian function and improves fertility rates in naturally senescent females.