Sperm DNA Integrity Assessment in Male Infertility

Summary

Sperm DNA integrity has emerged as a pivotal determinant of male reproductive potential, influencing fertilisation rates, embryo development and live-birth outcomes. Damage to sperm chromatin may take the form of single- or double-strand breaks, often precipitated by oxidative stress, abortive apoptosis or defects in chromatin remodelling during spermiogenesis. The protamine-rich packaging of sperm DNA confers a high degree of compaction but also limits intrinsic repair capacity, rendering sperm vulnerable to exogenous and endogenous insults. A spectrum of diagnostic assays—ranging from the Comet assay and TUNEL to Sperm Chromatin Dispersion and flow-cytometric detection of reactive oxygen species—allows quantification of DNA fragmentation and oxidative burden. Clinical guidelines now advocate incorporation of DNA integrity testing into the male infertility work-up, informing decisions on varicocele repair, antioxidant therapies, cryopreservation protocols and assisted conception strategies. Advances in assay standardisation, threshold definition and epigenetic profiling are broadening the scope of sperm DNA integrity assessment, with the ultimate aim of personalised reproductive care.

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Sperm DNA Integrity Assessment in Male Infertility publication trend

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Technical terms

Sperm DNA fragmentation: The presence of single- or double-stranded breaks in sperm nuclear DNA, compromising genetic integrity.

Reactive oxygen species (ROS): Chemically reactive molecules that can induce oxidative damage to sperm lipids, proteins and DNA.

TUNEL assay: A method for detecting DNA strand breaks by labelling free 3′-OH termini with fluorescent nucleotides.

Sperm Chromatin Dispersion (SCD) test: An assay that infers DNA fragmentation by measuring the size of chromatin halos released after acid denaturation.

Protamination: The replacement of histones with protamines during spermiogenesis, resulting in highly condensed sperm chromatin.

References

  1. Types, Causes, Detection and Repair of DNA Fragmentation in Animal and Human Sperm Cells. International Journal of Molecular Sciences (2012).
  2. Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress. Molecular Medicine (2015).
  3. Single and Double Strand Sperm DNA Damage: Different Reproductive Effects on Male Fertility. Genes (2019).
  4. Testicular and Haematological Cancer Induce Very High Levels of Sperm Oxidative Stress. Antioxidants (2023).
  5. Sperm Chromatin Dispersion Test Detects Sperm DNA Fragmentation Mainly Associated with Unviable Spermatozoa and Underestimates the Values with Respect to TUNEL Assay. International Journal of Molecular Sciences (2024).
  6. Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations. Andrologia (2020).

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