Oxygen delivery and fetal-placental growth: beyond a question of supply and demand?

Towards the end of the first trimester, blood flow and oxygenation rise within the placenta, supporting an increased capacity for mitochondrial oxidative metabolism in both the placenta and developing fetus. In this regard, the placenta acts uniquely as both a conduit of oxygen to the fetal circulation and a significant consumer of oxygen in order to support its own energy demands for the processes of nutrient transport and protein synthesis for hormone production and growth. When the supply of oxygen becomes restricted, for example during chronic exposure to hypobaric hypoxia at high altitude, placental and fetal tissues respond in order to optimise the allocation of oxygen between competing demands. In this case, the placenta appears to remodel its metabolism to decrease oxygen consumption, probably by increasing ATP production via glycolysis. This process can maintain oxygen supply to the fetus but is still associated with growth restriction. Oxidative stress, a feature of pre-eclampsia, might elicit similar metabolic changes in the absence of hypoxia. This review considers what is known about the metabolic response of the placenta and fetal tissues to hypoxia and oxidative stress, and suggests possible mechanisms that might underlie such metabolic remodelling using lessons from other tissues and organ systems. Aspects of the hypoxia response that remain to be addressed are highlighted and future studies suggested. Much remains unknown about the coordinated metabolic response of the fetal-placental unit to chronic hypoxia and oxidative stress, but it would appear to be more than a simple question of supply and demand.