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牛磺酸通过与TBK1相关的线粒体自噬减轻猪和小鼠排卵后卵母细胞的老化。

Taurine alleviates postovulatory oocyte aging via TBK1 associated mitophagy in pigs and mice.

作者信息

Zhang Fa-Li, Gao Chen-Xi, Li Wen-Wen, Li Ai-Ying, Li Lan, Shen Wei

机构信息

College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China; College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.

College of Life Sciences, Qingdao Agricultural University, Qingdao, 266109, China.

出版信息

Theriogenology. 2025 Oct 15;246:117531. doi: 10.1016/j.theriogenology.2025.117531. Epub 2025 Jun 11.

DOI:10.1016/j.theriogenology.2025.117531
PMID:40523328
Abstract

Taurine deficiency is a driver of aging, however the mechanisms by which taurine regulates postovulatory oocyte aging (POA) remain an unanswered question. Here, we used differential gene expressions and functional enrichment analysis of transcriptomes to determine transcriptional dynamics in POA. Transcriptional conservation between mouse and pig was determined by comparative analysis of transcriptomes. Candidate key targets were identified by WGCNA analysis combined with comparative analysis of transcriptomes. Expression levels were validated using cell-based immunofluorescence assays. We observed increased fragmentation and apoptosis of oocytes during POA, which was significantly improved after adding taurine. Transcriptome analysis showed that mitochondrial function was disrupted in oocytes. Our mitochondrial immunofluorescence assay showed that mitochondrial distribution in the POA group was abnormal compared with fresh group, and ROS levels were increased. Moreover, comparative analysis highlighted the role of mitophagy, and the immunofluorescence assay highlighted the significant decrease in PINK1. On the note, we combined comparative analysis and WGCNA results to identify TBK1 as a key gene, subsequent protein fluorescence confirmed that TBK1 was downregulated during POA. As expected, the taurine increased the expression level of TBK1 in the aged group. In summary, our evidence demonstrates that taurine can improve oocyte quality during POA via TBK1-associated mitophagy.

摘要

牛磺酸缺乏是衰老的一个驱动因素,然而牛磺酸调节排卵后卵母细胞衰老(POA)的机制仍是一个未解之谜。在这里,我们使用转录组的差异基因表达和功能富集分析来确定POA中的转录动态。通过转录组的比较分析确定了小鼠和猪之间的转录保守性。通过WGCNA分析结合转录组的比较分析鉴定了候选关键靶点。使用基于细胞的免疫荧光测定法验证表达水平。我们观察到POA期间卵母细胞的碎片化和凋亡增加,添加牛磺酸后显著改善。转录组分析表明卵母细胞中的线粒体功能受到破坏。我们的线粒体免疫荧光测定表明,与新鲜组相比,POA组中线粒体分布异常,ROS水平升高。此外,比较分析突出了线粒体自噬的作用,免疫荧光测定突出了PINK1的显著降低。值得注意的是,我们结合比较分析和WGCNA结果鉴定TBK1为关键基因,随后的蛋白质荧光证实POA期间TBK1下调。正如预期的那样,牛磺酸增加了衰老组中TBK1的表达水平。总之,我们的证据表明牛磺酸可以通过与TBK1相关的线粒体自噬改善POA期间的卵母细胞质量。

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