Embryonic metabolism of foetal fuels in whole-embryo culture.

The whole-embryo culture technique has been extensively used to evaluate embryonic growth and development using morphological criteria. However, the system also provides an opportunity to assess the status of embryonic metabolism to determine biochemical maturation and alterations induced by xenobiotics or changes in substrate availability. For example, using (14)C-labelled substrates the rates of product formation may be determined for a variety of foetal fuels such as glucose and the ketone body, beta-hydroxybutyrate. During organogenesis glucose metabolism is characterized by high rates of glycolytic metabolism at the early-somite stage and an increased dependence on Krebs cycle concomitant with the establishment of the chorioallantoic placenta (c. 30-somite stage) to initiate an increasingly 'foetal' type of pattern. The dependence of the neurulating embryo on glucose as a fuel is further demonstrated by the embryotoxic effects of insulin-induced hypoglycaemia. Although decreased glycolytic metabolism is the earliest effect of this treatment, both the Krebs cycle and oxidative pentose phosphate pathway are also inhibited. Therefore, the induction of malformations by hypoglycaemia is the result of a multifactorial biochemical alteration. In addition to glucose, mouse conceptuses have the capacity to metabolize alternative foetal fuels such as the ketone bodies d- and dl-BOHB at rates that are concentration dependent. However, the energy production from these substrates is limited by the low rates of Krebs-cycle metabolism at the early-somite stage.