Shaanxi Stem Cell Engineering and Technology Research Center, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Oxid Med Cell Longev. 2022 Feb 21;2022:7113793. doi: 10.1155/2022/7113793. eCollection 2022.
-Ketoglutarate (-KG) is a metabolite in the tricarboxylic acid cycle. It has a strong antioxidant function and can effectively prevent oxidative damage. Previous studies have shown that -KG exists in porcine follicles, and its content gradually increases as the follicles grow and mature. However, the potential mechanism of supplementation of -KG on porcine oocytes during in vitro maturation (IVM) has not yet been reported. The purpose of this study was to explore the effect of -KG on the early embryonic development of pigs and the mechanisms underlying these effects. We found that -KG can enhance the development of early pig embryos. Adding 20 M -KG to the in vitro culture medium significantly increased the rate of blastocyst formation and the total cell number. Compared with to that of the control group, apoptosis in blastocysts of the supplement group was significantly reduced. -KG reduced the production of reactive oxygen species and glutathione levels in cells. -KG not only improved the activity of mitochondria but also inhibited the occurrence of apoptosis. After supplementation with -KG, pig embryo pluripotency-related genes (OCT4, NANOG, and SOX2) and antiapoptotic genes (Bcl2) were upregulated. In terms of mechanism, -KG activates the Nrf2/ARE signaling pathway to regulate the expression of antioxidant-related targets, thus combating oxidative stress during the in vitro culture of oocytes. Activated Nrf2 promotes the transcription of Bcl2 genes and inhibits cell apoptosis. These results indicate that -KG supplements have a beneficial effect on IVM by regulating oxidative stress during the IVM of porcine oocytes and can be used as a potential antioxidant for IVM of porcine oocytes.
-酮戊二酸（-KG）是三羧酸循环中的一种代谢物。它具有很强的抗氧化功能，可有效防止氧化损伤。先前的研究表明，-KG 存在于猪卵泡中，其含量随着卵泡的生长和成熟而逐渐增加。然而，-KG 对猪卵母细胞体外成熟（IVM）的潜在补充机制尚未报道。本研究旨在探讨 -KG 对猪早期胚胎发育的影响及其作用机制。我们发现 -KG 可以增强早期猪胚胎的发育。在体外培养物中添加 20 μM -KG 可显著提高囊胚形成率和总细胞数。与对照组相比，补充组囊胚的凋亡率显著降低。-KG 减少了细胞中活性氧和谷胱甘肽的产生。-KG 不仅改善了线粒体的活性，而且抑制了细胞凋亡的发生。补充 -KG 后，猪胚胎多能性相关基因（OCT4、NANOG 和 SOX2）和抗凋亡基因（Bcl2）上调。就机制而言，-KG 激活 Nrf2/ARE 信号通路来调节抗氧化相关靶基因的表达，从而在卵母细胞体外培养过程中抵抗氧化应激。激活的 Nrf2 促进 Bcl2 基因的转录并抑制细胞凋亡。这些结果表明，-KG 通过调节猪卵母细胞体外成熟过程中的氧化应激对 IVM 有有益的影响，可作为猪卵母细胞体外成熟的潜在抗氧化剂。
