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Hum. Reprod. Advance Access published online on October 3, 2008

Human Reproduction, doi:10.1093/humrep/den346
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

DNA damage and metabolic activity in the preimplantation embryo

Roger G. Sturmey1, Judith A. Hawkhead, E. Ann Barker and Henry J. Leese

Biology Department (Area 3), University of York, York YO10 5YW, UK

1 Correspondence address. E-mail: r.g.sturmey{at}gmail.com

BACKGROUND: Embryos with greater viability have a lower or ‘quieter’ amino acid metabolism than those which arrest. We have hypothesized this is due to non-viable embryos possessing greater cellular/molecular damage and consuming more nutrients, such as amino acids for repair processes. We have tested this proposition by measuring physical damage to DNA in bovine, porcine and human embryos at the blastocyst stage and relating the data to amino acid profiles during embryo development.

METHODS: Amino acid profiles of in vitro-derived porcine and bovine blastocysts were measured by high-performance liquid chromatography and the data related retrospectively to DNA damage in each individual blastomere using a modified alkaline comet assay. Amino acid profiles of spare human embryos on Day 2–3 were related to DNA damage at the blastocyst stage.

RESULTS: A positive correlation between amino acid turnover and DNA damage was apparent when each embryo was examined individually; a relationship exhibited by all three species. There was no relationship between DNA damage and embryo grade.

CONCLUSIONS: Amino acid profiling of single embryos can provide a non-invasive marker of DNA damage at the blastocyst stage. The data are consistent with the quiet embryo hypothesis with viable embryos (lowest DNA damage) having the lowest amino acid turnover. Moreover, these data support the notion that metabolic profiling, in terms of amino acids, might be used to select single embryos for transfer in clinical IVF.

Key words: DNA damage/IVF/comet assay/amino acid profile/blastocyst

Submitted on May 28, 2008; resubmitted on July 8, 2008; accepted on August 8, 2008.


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