Role of developmental factors in the switch from pyruvate to glucose as the major exogenous energy substrate in the preimplantation mouse embryo

Preimplantation mouse embryos, cultured in vitro and those freshly flushed from the reproductive tract, exhibit a switch in energy substrate preferenc e, from pyruvate during the early preimplantation stages, to glucose at the blastocyst stage. Although the biochemical basis of this phenomenon is qui te well characterized its timing and possible association with developmenta l factors have not been considered. We have therefore examined the role of five developmental factors in determining the timing of the switch, namely: (I) embryo age tin hours post hCG); (2) developmental stage; (3) cytokines is; (4) cell number; and (5) activation of the embryonic genome. One-cell e mbryos, which develop more slowly than 2-cell embryos in vitro, were used t o investigate the role of embryo age and developmental stage. Cytochalasin D, which inhibits cytokinesis and delays the timing of compaction and cavit ation, was used to investigate the role of cell division and developmental stage. Finally, transcription of the embryonic genome was examined with the inhibitor, alpha-amanitin. Pyruvate and glucose consumption by single embr yos were measured using a noninvasive ultramicrofluorometric technique. The results showed that the timing of the switch in energy substrate preferenc e is precisely regulated in the mouse preimplantation embryo. Activation of the embryonic genome is a prerequisite for the switch and its timing is cl osely associated with developmental stage, specifically compaction and/or c avitation. Cell number, cytokinesis and embryo age appeared to be unrelated to the timing of the switch. These conclusions may well be extrapolated to other species, since an increase in net glucose uptake, if not always at t he expense of pyruvate, is a feature of preimplantation embryo metabolism i n all mammals studied.