Oxygen and placental development; parallels and differences with tumour biology

Human placentation involves the invasion of the conceptus into the wall of the uterus, and establishment of a blood supply from the maternal spiral arteries. The placenta has therefore been likened to a malignant tumour, albeit a highly regulated one. Oxygen plays an important role in controlling both placental development and tumour behaviour. In the placenta, early development takes place in a physiological low oxygen environment, which undergoes a transition with onset of the full maternal arterial circulation towards the end of the first trimester. By comparison, in tumours there is often a progressive hypoxia as the mass outgrows its blood supply. Both early placental tissues and tumour cells show high rates of proliferation, and the energy required to support these comes principally from glycolysis. Glycolysis is maintained in placental tissues by reoxidation of pyridine nucleotides through the polyol pathways, whereas in tumours there is fermentation to lactate, Warburg metabolism. In both cases, the reliance on glycolysis rather than oxidative phosphorylation preserves carbon skeletons that can be utilised in the synthesis of nucleotides, cell membranes and organelles, and that would otherwise be excreted as carbon dioxide. In the placenta, this reliance may also protect the embryo from free radical-mediated teratogenesis. Local oxygen gradients within both sets of tissues may influence the cell behaviour. In particular, they may induce an epithelial-mesenchymal transition, promoting extravillous trophoblast invasion in the placenta and metastasis in a tumour. Further investigations into the two scenarios may provide new insights of benefit to these contrasting, but similar, fields of cellular biology.