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Damage to Sperm DNA Mediated by Reactive Oxygen Species: Its Impact on Human Reproduction and the Health Trajectory of Offspring

  • Chapter
The Male Role in Pregnancy Loss and Embryo Implantation Failure

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 868))

Abstract

Disruptions to the genetic integrity of the mammalian spermatozoon play a major role in determining the subsequent developmental trajectory of the embryo. This chapter examines the causative links that connect DNA damage in human spermatozoa and the appearance of mutations in the progeny responsible for a variety of clinical conditions from autism to cancer. Integral to this discussion is an abundance of evidence indicating that human spermatozoa are vulnerable to free radical attack and the generation of oxidative DNA damage. The resolution of this damage appears to be initiated by the spermatozoa but is driven to completion by the oocyte in a round of DNA repair that follows fertilization. The persistence of unresolved oxidative DNA damage following zygote formation has the potential to create mutations/epimutations in the offspring that may have a profound impact on the health of the progeny. It is proposed that the creation of oxidative stress in the male germ line is a consequence of a wide variety of environmental/lifestyle factors that influence the health and well-being of the offspring as a consequence of mutational change induced by the aberrant repair of oxidative DNA damage in the zygote. Factors such as paternal age, subfertility, smoking, obesity, and exposure to a range of environmental influences, including radio-frequency electromagnetic radiation and xenobiotics, have all been implicated in this process. Identifying the contributors to oxidative stress in the germ line and resolving the mechanisms by which such stressors influence the mutational load carried by the progeny will be an important task for the future. This task is particularly pressing, given the extensive use of assisted reproductive technologies to achieve pregnancies in vitro that would have been prevented in vivo by the complex array of mechanisms that nature has put in place to ensure that only the fittest gametes participate in the generative process.

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Acknowledgments

We gratefully acknowledge the support given by the University of Newcastle and the National Health and Medical Research Council that has enabled the studies summarized in this chapter to be undertaken.

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Authors and Affiliations

  1. Priority Research Centre in Reproductive Science, University of Newcastle, Callaghan, NSW, 2308, Australia

    Dan Gavriliouk & Robert John Aitken Sc.D., F.R.S.E., F.A.A.

  2. Faculty of Health and Medicine, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, 2308, Australia

    Dan Gavriliouk & Robert John Aitken Sc.D., F.R.S.E., F.A.A.

  3. School of Environmental and Life Sciences, Discipline of Biological Sciences, University of Newcastle, University Drive, Callaghan, NSW, 2308, Australia

    Robert John Aitken Sc.D., F.R.S.E., F.A.A.

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  1. Dan Gavriliouk
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  2. Robert John Aitken Sc.D., F.R.S.E., F.A.A.
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Correspondence to Robert John Aitken Sc.D., F.R.S.E., F.A.A. .

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  1. Obstetrics, Gynecology, & Repro Medicine, Stony Brook University Medical Center T9-080, Stony Brook, New York, USA

    Richard Bronson

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Gavriliouk, D., Aitken, R.J. (2015). Damage to Sperm DNA Mediated by Reactive Oxygen Species: Its Impact on Human Reproduction and the Health Trajectory of Offspring. In: Bronson, R. (eds) The Male Role in Pregnancy Loss and Embryo Implantation Failure. Advances in Experimental Medicine and Biology, vol 868. Springer, Cham. https://doi.org/10.1007/978-3-319-18881-2_2

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