Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, 250012, Jinan, Shandong, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, 250012, Jinan, Shandong, China.
Cell Death Dis. 2020 Nov 11;11(11):965. doi: 10.1038/s41419-020-03183-5.
Maternal fertility declines irreversibly with aging, and advanced maternal age is mostly related to impaired oocyte quality. The flavonol compound quercetin is considered to be an anti-aging agent due to its cytoprotective actions as an antioxidant. However, its role and mechanisms on aged oocytes are unclear. In this study, the quercetin promotes in vitro maturation (IVM) and early embryonic development of oocytes from aged mice. It is extended these findings in human oocytes, showing that quercetin promotes the IVM rate by 19.6% and increases the blastocyst formation rate by 15.5% compared to untreated controls. The overall oocyte quality of aged mice is improved by quercetin treatment, assessed as spindle/chromosome morphology and cortical granule distribution. Mitochondria is the primary endogenous source of age-related oxidative stress, and an RNA-seq analysis of quercetin-treated oocytes reveals molecular insights including scavenged mitochondrial-ROS, reduced apoptosis, and improved autophagy. Further, this study demonstrates that quercetin reduces ROS via SIRT3-mediated acetylation of SOD2's K68 residue. Thus, beyond demonstrating that quercetin confers beneficial mitochondria-related impacts in aged oocytes, this study illustrates a potential strategy to prevent or delay oocyte aging and to improve success rates of assisted human reproductive technologies (ART).
母体生育能力会随着年龄的增长而不可逆地下降，而高龄产妇主要与卵母细胞质量受损有关。类黄酮化合物槲皮素因其抗氧化作用的细胞保护作用而被认为是一种抗衰老剂。然而，其在老化卵母细胞中的作用和机制尚不清楚。在这项研究中，槲皮素促进了来自老年小鼠的卵母细胞的体外成熟（IVM）和早期胚胎发育。将这些发现扩展到人类卵母细胞中，表明与未处理的对照组相比，槲皮素将 IVM 率提高了 19.6%，并将囊胚形成率提高了 15.5%。用槲皮素处理可改善老年小鼠卵母细胞的整体质量，评估方法为纺锤体/染色体形态和皮质颗粒分布。线粒体是与年龄相关的氧化应激的主要内源性来源，对槲皮素处理的卵母细胞进行 RNA-seq 分析揭示了分子见解，包括清除线粒体 ROS、减少细胞凋亡和改善自噬。此外，这项研究表明，槲皮素通过 SIRT3 介导的 SOD2 的 K68 残基乙酰化来减少 ROS。因此，本研究不仅证明了槲皮素赋予了老化卵母细胞有益的线粒体相关影响，还说明了一种预防或延迟卵母细胞衰老并提高辅助人类生殖技术（ART）成功率的潜在策略。
