The role of glucose and pyruvate transport in regulating nutrient utilization by preimplantation mouse embryos

Abstract

Preimplantation mouse embryos utilize pyruvate preferentially during the early cleavage stages before switching to glucose at around the time of compaction. This switch in substrate preference has been studied using a non-invasive ultramicrofluorometric analytical technique on single mouse embryos. On the basis of transport kinetic studies and inhibition by phloretin, cytochalasin B and sugar analogues, a component of glucose uptake by mouse blastocysts was found to be mediated by facilitated diffusion. The J(max) and K(t) of this facilitated component were 3.53 pmol embryo-1h-1 and 0.14 mM, respectively. At physiological concentrations of glucose, the facilitated component accounts for around 75% of glucose uptake. Glucose uptake by blastocysts was found to be insensitive to insulin, added at a range of concentrations. There was no evidence for glucose active transport. The carrier-mediated component of glucose entry was detectable from the 2-cell stage onwards. Pyruvate uptake was also mediated by a carrier throughout development. In the absence of glucose in the incubation medium, the characteristic decline in pyruvate uptake does not occur. The daya are consistent with a role for embryonic cell transport in regulating glucose utilization prior to compaction, but do not exclude the involvement of metabolic factors, such as the allosteric regulation of the enzymes hexokinase and phosphofructokinase.