Hypoxic Gene Regulation in Differentiating ES Cells

Mammalian development occurs in the hypoxic environment of the uterus (1 ,2 ). Initially, the limited oxygen available can adequately diffuse to all the cells of the growing conceptus. However, with continued growth, diffusion becomes less efficient and results in a “physiologic hypoxia” within the embryo (3 ). Current models suggest this physiologic hypoxia acts as a stimulus to coordinate the development of the cardiovascular system. Once formed, oxygen can be transported throughout the organism to enable aerobic respiration and promote increased ATP production. Unless the increasing energy demands of the embryo are met, further development will be halted, and early lethality will occur.