College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China.
Free Radic Biol Med. 2019 Nov 1;143:84-94. doi: 10.1016/j.freeradbiomed.2019.08.002. Epub 2019 Aug 6.
Postovulatory aging is known to compromise the oocyte quality as well as subsequent embryo development in many different animal models, and becomes one of the most intractable issues that limit the outcome of human assisted reproductive technology (ART). However, the strategies to prevent the deterioration of aged oocytes and relevant mechanisms are still underexplored. Here, we find that supplementation of CoQ10, a natural antioxidant present in human follicular fluids, is able to restore the postovulatory aging-induced fragmentation of oocytes and decline of fertilization. Importantly, we show that CoQ10 supplementation recovers postovulatory aging-caused meiotic defects such as disruption of spindle assembly, misalignment of chromosome, disappearance of actin cap, and abnormal distribution patterns of mitochondria and cortical granules. In addition, CoQ10 protects aged oocytes from premature exocytosis of ovastacin, cleavage of sperm binding site ZP2, and loss of localization of Juno, to maintain the fertilization potential. Notably, CoQ10 suppresses the aging-induced oxidative stress by reducing the levels of superoxide and DNA damage, ultimately inhibiting the apoptosis. Taken together, our findings demonstrate that CoQ10 supplementation is a feasible and effective way to prevent postovulatory aging and preserve the oocyte quality, potentially contributing to improve the successful rate of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) during human ART.
排卵后衰老已知会影响许多不同动物模型中的卵母细胞质量和随后的胚胎发育，并且成为限制人类辅助生殖技术（ART）结局的最棘手问题之一。然而，预防老化卵母细胞恶化的策略和相关机制仍未得到充分探索。在这里，我们发现补充 CoQ10（一种存在于人卵泡液中的天然抗氧化剂）能够恢复排卵后衰老引起的卵母细胞碎片化和受精能力下降。重要的是，我们表明 CoQ10 补充剂可恢复排卵后衰老引起的减数分裂缺陷，如纺锤体组装中断、染色体排列不齐、肌动蛋白帽消失以及线粒体和皮质颗粒的异常分布模式。此外，CoQ10 可保护老化卵母细胞免受卵母细胞蛋白水解酶 ovastacin 的过早胞吐、精子结合位点 ZP2 的切割以及 Juno 定位的丢失，从而维持受精潜能。值得注意的是，CoQ10 通过降低超氧化物和 DNA 损伤的水平来抑制衰老引起的氧化应激，最终抑制细胞凋亡。总之，我们的研究结果表明，CoQ10 补充剂是一种可行且有效的预防排卵后衰老和保持卵母细胞质量的方法，可能有助于提高人类 ART 中体外受精（IVF）和胞浆内单精子注射（ICSI）的成功率。
