During early mammalian embryogenesis, the developing embryo must adapt to changing metabolic demands and substrate availability. It has long been thought that a metabolic shift from glycolysis to OXPHOS takes place during this period and may be linked to the onset of choroallantoic branching, a major milestone in placental development that increases nutrient availability via the maternal circulation. But a simple shift from glycolysis to OXPHOS cannot explain how the array of macromolecules that are required to fuel cell proliferation are made, since OXPHOS produces mainly cellular energy and little else. Now, on p. 63, Yoshifumi Yamaguchi, Masayuki Miura and colleagues revisit this theory using state-of-the-art mass spectrometry techniques to survey the carbon flow of intracellular metabolites in the whole mouse embryo from embryonic day (E) 8.5 to E10.5, the period in which extensive choroallantoic branching occurs. The authors first establish the metabolic profile of the embryo during this period and show that, while metabolites indicative of OXPHOS do increase over this period, this is not accompanied by a decrease in glycolysis. Rather, the end product of glycolysis, lactate, also increases markedly from E8.5 to E10.5. The authors observe a decrease in the activity of phosphofructokinase-1 and go on to show how this results in the redirection of glucose into the pentose phosphate pathway, which is key for biomass production. This study provides insight into the dynamic metabolic profile of the developing embryo and sheds light on the long-standing question of whether and how a metabolic shift occurs during choroallantoic branching.
