Cai Yelan, Ma Jiawei, Xu Haifeng, Jian Huamei, Gao Wenyi, Wu Man, Liu Bailin, Chen Ying
Institute of Medical Genetics, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, 214002, China.
The 904th, Hospital of Joint Logistic Support Force of PLA, Wuxi, 214002, China.
Reprod Sci. 2025 Aug 27. doi: 10.1007/s43032-025-01959-8.
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.
卵巢衰老导致卵母细胞质量下降和生殖潜能降低，这是辅助生殖技术（ART）面临的主要挑战之一。氧化应激（OS）是导致这种下降的主要因素。在本研究中，我们调查了天然黄酮类化合物甘草素（LQ）对老龄小鼠卵母细胞成熟和胚胎发育的保护作用。结果表明，20 μM LQ显著提高了老龄卵母细胞的成熟率，恢复了纺锤体形态，并提高了受精率和二细胞胚胎发育率。机制研究发现，LQ降低了卵母细胞中活性氧（ROS）的水平，并恢复了线粒体功能，包括分布模式和膜电位。此外，LQ上调了老龄小鼠卵巢和卵母细胞以及人卵巢颗粒细胞瘤细胞系（KGN）中沉默调节蛋白1（SIRT1）和核因子E2相关因子2（NRF2）的蛋白表达。尽管其mRNA水平变化极小，但表明它可能通过翻译后调控发挥作用。这些结果表明，LQ通过激活SIRT1/NRF2信号通路保护老龄卵母细胞免受氧化应激，突出了其作为天然抗氧化剂缓解卵巢衰老和提高卵母细胞质量的潜力。
