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Origins of Sperm DNA Damage

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Male Infertility

Abstract

Male infertility is increasing in recent decades, affecting 7% of males during their reproductive life. The standard semen analysis remains widely used, specifically sperm concentration, motility, viability, and normal sperm morphology. However, this analysis is limited in clinical usefulness without information of the functional capacity of the spermatozoa. Increased DNA fragmentation in spermatozoa is associated with over 80% of male infertility cases. Numerous pathologies associated with male infertility have a detrimental effect on spermatozoa chromatin condensation and DNA integrity through the spermatogenesis pathways, epididymal maturation, and post-ejaculations. Spermatozoa DNA damage is the consequence of modifications of the molecular structure of the DNA, causing structural changes in the DNA that prevents replication mechanisms from optimal functioning. The determination of DNA fragmentation or damage in spermatozoa has emerged as a stable parameter with lower variability and better predictability for infertility, pregnancy complications, and health outcomes of the offspring. Mechanisms of DNA modifications include chemical modification of bases such as 8-oxo-2′-doxyguanosine (8-OHdG), single-strand breaks, double-strand breaks, base missing from the DNA backbone, modifications in purine, pyrimidine, and deoxyribose, introduction of a basic sites, and DNA cross-linking. Origins of DNA damage include endogenous causes, predominantly associated with ROS. Exogenous DNA damage is caused by radiation, genital heat stress, toxins, or mutagenic exposure. Pathology and risk factors associated with causing DNA fragmentation include varicocele, scrotal hyperthermia, genital tract infections and leukocytospermia, poor lifestyle habits, obesity and diabetes, environmental toxins, cancer and chemotherapy, radiation, medications, and aging. These are mediated through inflammation, ROS, chromatin remodeling, and increased apoptosis in germ cell lines and spermatozoa. However, more research into the causes and mechanisms of DNA fragmentation is recommended, as well as standardization of appropriate assessment tools.

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Authors and Affiliations

  1. American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, Cleveland, OH, USA

    Ralf Henkel

  2. Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa

    Ralf Henkel

  3. School of Natural Medicine, University of the Western Cape, Bellville, South Africa

    Kristian Leisegang

Authors
  1. Ralf Henkel
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  2. Kristian Leisegang
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Correspondence to Ralf Henkel .

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Editors and Affiliations

  1. PUR Clinic, University of Central Florida (UCF), Clermont, FL, USA

    Sijo J. Parekattil

  2. ANDROFERT and State University of Campinas (UNICAMP), Campinas, Brazil

    Sandro C. Esteves

  3. Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Ashok Agarwal

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Henkel, R., Leisegang, K. (2020). Origins of Sperm DNA Damage. In: Parekattil, S., Esteves, S., Agarwal, A. (eds) Male Infertility. Springer, Cham. https://doi.org/10.1007/978-3-030-32300-4_29

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  • DOI: https://doi.org/10.1007/978-3-030-32300-4_29

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-32299-1

  • Online ISBN: 978-3-030-32300-4

  • eBook Packages: MedicineMedicine (R0)

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