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Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytes

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Abstract

Chromosome segregation errors are a significant cause of aneuploidy among human neonates and often result from errors in female meiosis that occur during fetal life. For the latter reason, little is known about chromosome dynamics during female prophase I. Here, we analyzed chromosome reorganization, and centromere and telomere dynamics in meiosis in the human female by immunofluorescent staining of the SYCP3 and SYCP1 synaptonemal complex proteins and the course of recombinational DNA repair by IF of phospho-histone H2A.X (γ-H2AX), RPA and MLH1 recombination proteins. We found that SYCP3, but not SYCP1, aggregates appear in the preleptotene nucleus and some persist up to pachytene. Telomere clustering (bouquet stage) in oocytes lasted from late-leptotene to early pachytene—significantly longer than in the male. Leptotene and zygotene oocytes and spermatocytes showed strong γ-H2AX labeling, while γ-H2AX patches, which colocalized with RPA, were present on SYCP1-tagged pachytene SCs. This was rarely seen in the male and may suggest that synapsis installs faster with respect to progression of recombinational double-strand break repair or that the latter is slower in the female. It is speculated that the presence of γ-H2AX into pachytene highlights female-specific peculiarities of recombination, chromosome behavior and checkpoint control that may contribute to female susceptibility for aneuploidy.

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Acknowledgements

We thank Dr. C. Heyting for kindly providing SYCP antibodies. This work was carried out with financial support from FIS 02/0297, Fundación Salud 2000-Ayudas Serono and SGR-00201. I.R. is the recipient of a grant (AP2000) from the Ministerio de Educación, Cultura y Deporte. We are grateful to unidentified reviewers for their stimulating comments on an earlier draft of this paper. H.S. thanks H.H. Ropers (MPI-MG, Berlin) and the DFG (Grant no. SCHE 350/8-4) for support.

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Authors and Affiliations

  1. Dept. de Biol. Cellular, Fisiologia i Immunologia, Univ. Autònoma de Barcelona, 08193, Bellaterra, Spain

    I. Roig, J. Egozcue & M. Garcia

  2. Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195, Berlin, Germany

    B. Liebe & H. Scherthan

  3. Servei de Ginecologia i Obstetrícia, Hospital Materno-Infantil de la Vall d’Hebron, Barcelona, Spain

    Ll. Cabero

  4. Inst. for Radiation Biology Bundeswehr, Neuherbergstrasse 11, 80937, Munich, Germany

    H. Scherthan

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  1. I. Roig
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  2. B. Liebe
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  3. J. Egozcue
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  4. Ll. Cabero
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  5. M. Garcia
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  6. H. Scherthan
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Correspondence to M. Garcia or H. Scherthan.

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Communicated by E.A. Nigg

I. Roig and B. Liebe made an equal contribution to this work

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Roig, I., Liebe, B., Egozcue, J. et al. Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytes. Chromosoma 113, 22–33 (2004). https://doi.org/10.1007/s00412-004-0290-8

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