A genetically defined animal model of anembryonic pregnancy

Mutant mouse conceptuses, homozygous for a defect in the gene encoding the glycolytic enzyme, glucose phosphate isomerase (GPI) died in utero by 9 1/2 days post coitum. By this stage there was no normal embryo, but trophoblast and some extra-embryonic membranes usually survived. The morphology of these genetically determined, anembryonic conceptuses was similar to some of the sporadic cases of anembryonic conceptuses that occurred in control crosses. These similarities suggest that an understanding of the cause of death of the homozygous mutant embryos might shed light on the aetiology of some of the cases of sporadic anembryonic conceptuses in both mouse and man. At implantation, the conceptus depends on anaerobic glycolysis for its energy production and any shortage of substrates would compromise development. It is argued that, in the absence of efficient glycolysis, a homozygous null embryo would be unable to produce sufficient energy to develop normally beyond the egg cylinder stage. However, the outer part of the conceptus might survive if nutrients and oxygen were available from the surrounding maternal tissue to produce energy by the aerobic tricarboxylic acid cycle. The homozygous GPI-null conceptuses may provide a useful animal model for some types of human anembryonic pregnancy.