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Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays

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Abstract

Purpose

To determine the level of expression for mRNAs that regulate DNA repair activity in oocytes at the germinal vesicle (GV) stage. Reactive oxygen species (ROS) have been shown to play a major role in the appearance of deleterious DNA decays, and this study focuses on the repair of damage linked to decay caused by the action of ROS. The oocyte needs a mechanism for repairing DNA decays in the early preimplantation embryo before the onset of genomic activation, since in the absence of repair, residual DNA damage would lead to either apoptosis or tolerance. Tolerance of DNA damage is a source of potential mutations.

Method

GV oocytes were selected for this study, both for the ethical reason that they are unsuitable for patient treatment, and because no transcription takes place during the period from GV to MII and then prior to genomic activation. The GV oocyte is therefore a good model for looking at DNA during the first cleavages of early preimplantation development. Six cohorts of GV oocytes were pooled for extraction of mRNA; the DNA was analysed using Affimetrix HG-UG133 Plus 2, containing 54,675 probe sets; spike and housekeeping genes were also added as internal controls.

Results

In GV oocytes, DNA repair pathways for oxidized bases are redundant. One step repair procedure (OSR), BER (base excision repair), MMR (mismatch repair) and NER (Nucleotide excision repair) are present. All the recognition proteins are also present. The chromatin assembly factors necessary for the maintenance of genomic stability are highly expressed.

Conclusion

Gene expression analysis shows that the oocyte does not allow a high level of tolerance for DNA decays. This regulatory mechanism should avoid transmitting mutations into the next generation.

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Acknowledgment

We would like to thank Dr Martine Dumont and Dr Anne Marie Junca for the generous gift of GV oocytes. Dr Soularue (Partnerchips) is acknowledged for his help in the realization of the project.

This work was sponsored by Organon France.

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Authors and Affiliations

  1. UNILABS, 12 Place Cornavin, Geneva, Switzerland

    Yves Jr Menezo

  2. Laboratoire d’Eylau, 55 Rue St Didier, 75116, Paris, France

    Yves Jr Menezo

  3. National Research Council, 83100, Avellino, Italy

    GianLuigi Russo

  4. Stazione Zoologica, Villa Communale 1, Napoli, Italy

    Elisabetta Tosti

  5. ATL R&D. Reproductive Biology & Genetics Laboratory, 78320, La Verrière, France

    Said El Mouatassim & Moncef Benkhalifa

  6. UNILABS/Laboratoire d’Eylau, 55 rue St Didier, 75116, Paris, France

    Yves Jr Menezo

Authors
  1. Yves Jr Menezo
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  2. GianLuigi Russo
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  3. Elisabetta Tosti
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  4. Said El Mouatassim
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  5. Moncef Benkhalifa
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Correspondence to Yves Jr Menezo.

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Menezo, Y.J., Russo, G., Tosti, E. et al. Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays. J Assist Reprod Genet 24, 513–520 (2007). https://doi.org/10.1007/s10815-007-9167-0

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  • DOI: https://doi.org/10.1007/s10815-007-9167-0

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