Bradley Josephine, Swann Karl
School of Biosciences, Cardiff University, UK.
Int J Dev Biol. 2019;63(3-4-5):93-103. doi: 10.1387/ijdb.180355ks.
Mammalian oocytes and early cleavage-stage embryos are critically dependent on their ˜100,000 mitochondria to develop from ovulation to compacted morula stage. They rely almost solely on oxidative phosphorylation of multiple intracellular substrates- namely pyruvate, fatty acids and glutamine- for production of ATP. Increasing evidence exists for the requirement of both fatty acids and pyruvate for mammalian developmental potential. Fatty acids are stored as neutral lipids in lipid droplets, which are liberated into the cytoplasm as free fatty acids and taken up into mitochondria for metabolism. Different mammalian species exhibit different amounts of stored and free lipid, while the types of lipid present tend to remain constant. It is thought that the amount of lipid contained in the oocytes of mammalian species reflects the extent of β-oxidation, but it is unclear why large differences are seen in lipid content. Maternal high fat diet or obesity causes negative intracellular effects such as the ER stress response, and oxidative mitochondrial and DNA damage. While some mechanisms have been established, it is still unclear exactly how high fat leads to compromised oocyte and embryo quality. It is proposed that healthy mammalian oocyte mitochondria require a balance of pyruvate and fatty acid oxidation in order to maintain a low level of otherwise damaging ROS production. This balance is disrupted in conditions of excess or insufficient substrate.
哺乳动物的卵母细胞和早期卵裂期胚胎从排卵发育到致密桑椹胚阶段严重依赖其约10万个线粒体。它们几乎完全依靠多种细胞内底物（即丙酮酸、脂肪酸和谷氨酰胺）的氧化磷酸化来产生ATP。越来越多的证据表明，脂肪酸和丙酮酸对于哺乳动物的发育潜能都是必需的。脂肪酸以中性脂质的形式储存在脂滴中，脂滴以游离脂肪酸的形式释放到细胞质中，并被线粒体摄取进行代谢。不同的哺乳动物物种表现出不同数量的储存脂质和游离脂质，而存在的脂质类型往往保持不变。人们认为，哺乳动物物种卵母细胞中所含脂质的量反映了β-氧化的程度，但尚不清楚为何脂质含量会出现巨大差异。母体高脂饮食或肥胖会导致细胞内产生负面效应，如内质网应激反应以及线粒体和DNA氧化损伤。虽然已经确立了一些机制，但仍不清楚高脂肪究竟是如何导致卵母细胞和胚胎质量受损的。有人提出，健康的哺乳动物卵母细胞线粒体需要丙酮酸和脂肪酸氧化之间的平衡，以维持较低水平的、否则会造成损害的活性氧生成。在底物过量或不足的情况下，这种平衡会被打破。
