Stunted by Developing in Hypoxia: Linking Comparative and Model Organism Studies

Abstract

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, in most 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.