Li Yu, Miao Yilong, Chen Jingyue, Xiong Bo
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Front Cell Dev Biol. 2021 Feb 25;9:625540. doi: 10.3389/fcell.2021.625540. eCollection 2021.
SIRT6, the sixth member of the sirtuin family proteins, has been characterized as a crucial regulator in multiple molecular pathways related to aging, including genome stability, DNA damage repair, telomere maintenance, and inflammation. However, the exact roles of SIRT6 during female germ cell development have not yet been fully determined. Here, we assessed the acquisition of meiotic competency of porcine oocytes by inhibition of SIRT6 activity. We observed that SIRT6 inhibition led to the oocyte meiotic defects by showing the impairment of polar body extrusion and cumulus cell expansion. Meanwhile, the compromised spindle/chromosome structure and actin dynamics were also present in SIRT6-inhibited oocytes. Moreover, SIRT6 inhibition resulted in the defective cytoplasmic maturation by displaying the disturbed distribution dynamics of cortical granules and their content ovastacin. Notably, we identified that transcript levels of genes related to oocyte meiosis, oxidative phosphorylation, and cellular senescence were remarkably altered in SIRT6-inhibited oocytes by transcriptome analysis and validated that the meiotic defects caused by SIRT6 inhibition might result from the excessive reactive oxygen species (ROS)-induced early apoptosis in oocytes. Taken together, our findings demonstrate that SIRT6 promotes the porcine oocyte meiotic maturation through maintaining the redox homeostasis.
沉默调节蛋白6（SIRT6）是沉默调节蛋白家族蛋白的第六个成员，已被确定为与衰老相关的多种分子途径中的关键调节因子，包括基因组稳定性、DNA损伤修复、端粒维持和炎症。然而，SIRT6在雌性生殖细胞发育过程中的具体作用尚未完全确定。在此，我们通过抑制SIRT6活性来评估猪卵母细胞减数分裂能力的获得情况。我们观察到，SIRT6抑制导致卵母细胞减数分裂缺陷，表现为极体排出和卵丘细胞扩展受损。同时，SIRT6抑制的卵母细胞中纺锤体/染色体结构和肌动蛋白动力学也受到损害。此外，SIRT6抑制通过显示皮质颗粒及其内容物卵母细胞溶素的分布动态紊乱，导致细胞质成熟缺陷。值得注意的是，我们通过转录组分析发现，SIRT6抑制的卵母细胞中与卵母细胞减数分裂、氧化磷酸化和细胞衰老相关的基因转录水平发生了显著变化，并证实SIRT6抑制引起的减数分裂缺陷可能是由卵母细胞中过量的活性氧（ROS）诱导的早期凋亡所致。综上所述,我们的研究结果表明，SIRT6通过维持氧化还原稳态促进猪卵母细胞减数分裂成熟。
