College of Life Sciences, Inner Mongolia University, Hohhot 010070, China.
College of Life Sciences and Technology, Inner Mongolia Normal University, Hohhot 010022, China.
Int J Mol Sci. 2023 Jan 4;24(2):924. doi: 10.3390/ijms24020924.
Ovarian organoids, based on mouse female germline stem cells (FGSCs), have great value in basic research and are a vast prospect in pre-clinical drug screening due to their properties, but the competency of these in vitro-generated oocytes was generally low, especially, in vitro maturation (IVM) rate. Recently, it has been demonstrated that the 3D microenvironment triggers mitochondrial dysfunction during follicle growth in vitro. Therefore, therapies that protect mitochondria and enhance their function in oocytes warrant investigation. Here, we reported that exposure to 100 nM MitoQ promoted follicle growth and maturation in vitro, accompanied by scavenging ROS, reduced oxidative injury, and restored mitochondrial membrane potential in oocytes. Mechanistically, using mice granulosa cells (GCs) as a cellular model, it was shown that MitoQ protects GCs against HO-induced apoptosis by inhibiting the oxidative stress pathway. Together, these results reveal that MitoQ reduces oxidative stress in ovarian follicles via its antioxidative action, thereby protecting oocytes and granulosa cells and providing an efficient way to improve the quality of in vitro-generated oocytes.
基于小鼠雌性生殖干细胞 (FGSCs) 的卵巢类器官在基础研究中有很大的价值,并且由于其特性,在临床前药物筛选中有广阔的前景,但这些体外生成的卵母细胞的能力通常较低,特别是体外成熟 (IVM) 率。最近,已经证明 3D 微环境在体外卵泡生长过程中触发线粒体功能障碍。因此,保护线粒体并增强卵母细胞中线粒体功能的治疗方法值得研究。在这里,我们报道了暴露于 100 nM MitoQ 可促进体外卵泡生长和成熟,同时清除 ROS、减少氧化损伤,并恢复卵母细胞中的线粒体膜电位。在机制上,使用小鼠颗粒细胞 (GCs) 作为细胞模型,表明 MitoQ 通过抑制氧化应激途径来保护 GCs 免受 HO 诱导的凋亡。总之,这些结果表明 MitoQ 通过其抗氧化作用减少卵巢卵泡中的氧化应激,从而保护卵母细胞和颗粒细胞,并提供了一种有效提高体外生成卵母细胞质量的方法。