ROLE OF GLUCOSE IN MOUSE PREIMPLANTATION EMBRYO DEVELOPMENT

Mouse preimplantation embryos consume pyruvate preferentially during t he early developmental stages, before glucose becomes the predominant energy substrate in the blastocyst. To investigate the importance of t he switch to glucose utilization at the later developmental stages, mo use embryos from F1 hybrid mice (CBA/Ca x C57BL/6) were cultured from the one- and two-cell stages (22 and 46 h post hCG, respectively) for 5 days in a modified medium, M16, containing 0.33 mM pyruvate and 5 or 23 mM D+L-lactate, in the presence and absence of 1 mM glucose (M16+G and M16-G, respectively). Nutrient uptakes were also determined over this time. Some embryos cultured in M16-G were transferred to M16+G at 94 or 118 h post hCG. Embryos cultured from the two-cell stage in M16 +G exhibited the characteristic fall in pyruvate consumption between t he morula and the blastocyst stage; those cultured from the two-cell s tage in M16-G compensated for the lack of glucose by consuming increas ing amounts of pyruvate, from 2.78 pmol/embryo/h at 58 h post hCG to 5 .21 pmol/embryo/h at 154 h post hCG. However, the percentage of embryo s developing to the blastocyst stage, the hatching rate, and blastocys t cell numbers (50.6+/-2.5 [28] vs. 105+/-3.8 [37]) were all lower in this group. When exposed to glucose at 94 or 118 h post hCG, embryos c ultured from the two-cell stage in M16-G readily consumed glucose in p reference to pyruvate, although the characteristic fall in pyruvate co nsumption was not observed. One-cell embryos cultured continuously in M16-G were only able to develop to the morula stage, after which time they degenerated. In these embryos pyruvate was readily consumed betwe en 22 and 94 h post hCG, before falling from 2.77 pmol/embryo/h at 83 h post hCG to 0.045 pmol/embryo/h at 130 h post hCG. Transfer of these embryos to M16+G at 94 and 118 h post hCG did not support development to the hatching blastocyst stage. The results show that mouse preimpl antation embryos from F1 hybrid mice (CBA/Ca x C57BL/6) need only be e xposed to glucose for less than 24 h between 22 and 94 h post hCG in o rder to develop from the morula to the blastocyst stage in vitro. Howe ver, the exposure time needs to be increased to between 24 and 72 h in order that blastocyst cell numbers reach control levels. The importan ce of glucose before the morula stage may relate to the need to synthe size glycogen for later use. If the obligatory requirement for glucose is fulfilled, embryos are able to utilize pyruvate in the absence of glucose at the later stages of development. These results show that th e mouse preimplantation embryo can, to some extent, adapt metabolicall y to changes in its external environment. (C) 1995 Wiley-Liss, Inc.