Liquiritigenin Restores Declined Oocyte Quality and Improves Embryo Development in Aged Mice

Ovarian aging leads to a decline in oocyte quality and reduced reproductive potential, which is one of the main challenges faced by assisted reproductive technology (ART). Oxidative stress (OS) is a major contributor to this decline. In this study, we investigated the protective effects of natural flavonoid compound liquiritigenin (LQ) on oocyte maturation and embryo development in aged mice. The results showed that 20 μM LQ significantly improved the maturation rate of aged oocytes, restored spindle morphology, and enhanced fertilization and two-cell embryo development rates. Mechanism studies have found that LQ reduces the levels of reactive oxygen species (ROS) in oocytes and restores mitochondrial function, including distribution patterns and membrane potential. Additionally, LQ upregulated the protein expression of Sirtuin 1 (SIRT1) and nuclear factor E2-related factor 2 (NRF2) in the ovaries and oocytes of aging mice, as well as in the human ovarian granulosa tumor cell line (KGN). Although its mRNA level showed minimal change, it suggested that it might play a role through post-translational regulation. These results suggest that LQ protects aged oocytes from oxidative stress by activating the SIRT1/NRF2 signaling pathway, highlighting its potential as a natural antioxidant for alleviating ovarian aging and improving oocyte quality.