Mitochondria and lipid metabolism in mammalian oocytes and early embryos

Abstract

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.