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. 2023 Apr;40(4):745-751.
doi: 10.1007/s10815-023-02748-5. Epub 2023 Feb 24.

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

Juan G Alvarez  1 , Agustin García-Peiró  2 , Alberto Barros  3   4   5 , Luís Ferraz  6 , Mário Sousa  7   8 , Denny Sakkas  9
Affiliations

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

Juan G Alvarez et al. J Assist Reprod Genet. 2023 Apr.

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.

Keywords: DNA repair; Double strand DNA breaks; Sperm DNA; Testicular sperm.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Consequences of fertilization by a sperm carrying double-strand breaks (DSB) in relation to the threshold of repair by the oocyte during fertilization. High levels of remaining DNA damage in the oocyte will lead to failure at earlier stages of development (fertilization or embryo), while lower levels of remaining DNA damage may manifest themselves later in development
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