Stunted by developing in hypoxia: Linking comparative and model organism studies

Animals develop in atmospheric hypoxia in a wide range of habitats, and tissues may experience O₂ limitation of ATP production during postembryonic development if O₂ supply structures do not keep pace with growing O₂ demand during ontogeny. Most animal species are stunted by postembryonic development in hypoxia, showing reduced growth rates and size in moderate hypoxia (5-15 kPa Po₂). In mammals, the critical Po₂ that limits resting metabolic rate also falls in this same moderate hypoxic range, so stunted growth may simply be due to hypoxic limits on ATP production. However, inmost invertebrates and at least some lower vertebrates, hypoxic stunting occurs at Po₂ values well above those that limit resting metabolism. Studies with diverse model organisms have identified multiple homologous O₂-sensing signaling pathways that can inhibit feeding and growth during moderate hypoxia. Together, these comparative and model organism-based studies suggest that hypoxic stunting of growth and size can occur as programmed inhibition of growth, often by inhibition of insulin stimulation of growth processes. Furthermore, there is increasing evidence that these same O₂ signaling pathways can be utilized during normal animal development to ensure matching of O₂ supply and demand structures and in mediation of variation in animal performance.