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Double strand DNA breaks in sperm: the bad guy in the crowd

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Abstract

Purpose

The main objective of this opinion paper was to bring to light and enhance our understanding of the amount of double-strand DNA breaks in sperm and whether there is a threshold of no return when considering repair by the oocyte/embryo.

Methods

A brief review of literature related to the theories proposed for the appearance of double-strand breaks in human spermatozoa. Further commentary regarding their detection, how oocytes or embryos may deal with them, and what are the consequences if they are not repaired. Finally, a strategy for dealing with patients who have higher levels of double-strand DNA breaks in sperm is proposed by reviewing and presenting data using testicular extracted sperm.

Results

We propose a theory that a threshold may exist in the oocyte that allows either complete or partial DNA repair of impaired sperm. The closer that an embryo is exposed to the threshold, the more the effect on the ensuing embryo will fail to reach various milestones, including blastocyst stage, implantation, pregnancy loss, an adverse delivery outcome, or offspring health. We also present a summary of the role that testicular sperm extraction may play in improving outcomes for couples in which the male has a high double-strand DNA break level in his sperm.

Conclusions

Double-strand DNA breaks in sperm provide a greater stress on repair mechanisms and challenge the threshold of repair in oocytes. It is therefore imperative that we improve our understanding and diagnostic ability of sperm DNA, and in particular, how double-strand DNA breaks originate and how an oocyte or embryo is able to deal with them.

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Authors and Affiliations

  1. Centro de Infertilidad Masculina ANDROGEN, La Coruña, Spain

    Juan G. Alvarez

  2. Centro de Infertilidad Masculina y Análisis de Barcelona (CIMAB), Barcelona, Spain

    Agustin García-Peiró

  3. Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal

    Alberto Barros

  4. Centro de Genética da Reprodução Alberto Barros, Porto, Portugal

    Alberto Barros

  5. Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal

    Alberto Barros

  6. Department of Urology, Hospital Centre of Vila Nova de Gaia/Espinho, Unit 1, Rua Conceição Fernandes 1079, 4434-502, Vila Nova de Gaia, Portugal

    Luís Ferraz

  7. Laboratory of Cell Biology, Department of Microscopy, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal

    Mário Sousa

  8. UMIB-Unit for Multidisciplinary Research in Biomedicine/ITR-Laboratory for Integrative and Translational Research in Population Health, University of Porto, Porto, Portugal

    Mário Sousa

  9. Boston IVF—Eugin Group, Boston, MA, USA

    Denny Sakkas

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  1. Juan G. Alvarez
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Alvarez, J.G., García-Peiró, A., Barros, A. et al. Double strand DNA breaks in sperm: the bad guy in the crowd. J Assist Reprod Genet 40, 745–751 (2023). https://doi.org/10.1007/s10815-023-02748-5

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