DNA damage and metabolic activity in the preimplantation embryo

BACKGROUND: Embryos with greater viability have a lower or ‘quieter’amino acid metabolism than those which arrest. We have hypothesizedthis is due to non-viable embryos possessing greater cellular/moleculardamage and consuming more nutrients, such as amino acids forrepair processes. We have tested this proposition by measuringphysical damage to DNA in bovine, porcine and human embryosat the blastocyst stage and relating the data to amino acidprofiles during embryo development. METHODS: Amino acid profiles of in vitro-derived porcine and bovine blastocystswere measured by high-performance liquid chromatography andthe data related retrospectively to DNA damage in each individualblastomere using a modified alkaline comet assay. Amino acidprofiles of spare human embryos on Day 2–3 were relatedto DNA damage at the blastocyst stage. RESULTS: A positive correlation between amino acid turnover and DNA damagewas apparent when each embryo was examined individually; a relationshipexhibited by all three species. There was no relationship betweenDNA damage and embryo grade. CONCLUSIONS: Amino acid profiling of single embryos can provide a non-invasivemarker of DNA damage at the blastocyst stage. The data are consistentwith the quiet embryo hypothesis with viable embryos (lowestDNA damage) having the lowest amino acid turnover. Moreover,these data support the notion that metabolic profiling, in termsof amino acids, might be used to select single embryos for transferin clinical IVF.