Ovine fetal leucine kinetics and protein metabolism during decreased oxygen availability

The fetus depends on an uninterrupted supply of oxygen to provide energy, not only for basal metabolism but also for the metabolic costs of growth. By curtailing the metabolically expensive processes of protein turnover, the fetus could conserve energy when oxygen availability is limited. Therefore, this investigation was performed to find whether protein synthesis and breakdown are diminished during decreased fetal oxygen availability. Furthermore, if these conditions reduce fetal growth, protein synthesis should be affected more than breakdown so that protein accretion, an important component of fetal growth, also falls. In eight chronically prepared fetal lambs, we compared leucine kinetics (reciprocal pool model) during control conditions with measurements made during maternal hypoxia, a condition that limits fetal oxygen availability. Decreased fetal oxygen availability (-43%; P < 0.001) reduced fetal oxygen consumption (-16%; P < 0.01), as well as both the uptake of leucine across the placenta (-48%; P < 0.001) and its rate of decarboxylation (-30%; P < 0.001). Fetal protein synthesis decreased (-32%; P < 0.001) to a greater extent than proteolysis (-22%; P < 0.001). Consequently, fetal protein accretion, an important component of fetal growth, also decreased (-62%; P < 0.001). We calculate that the reduction in fetal protein synthesis and breakdown, both processes that require intracellular expenditure of ATP, decreased fetal energy needs sufficiently to account for most, if not all, of the decrease measured in fetal oxygen consumption.