Strong Correlation Between Double-Strand DNA Breaks and Total Sperm DNA Fragmentation in the Human Ejaculate

Background: Double- and single-strand DNA breaks (DSBs and SSBs, respectively) in spermatozoa, which emerge from intrinsic and extrinsic degenerative processes, are likely related to the underlying male pathology.

Aim: To determine whether the incidence of DSBs in the human ejaculate is a consistent predictor of whole sperm DNA fragmentation (W-SDF = SSBs + DSBs).

Methods: A correlation between the proportion of spermatozoa that showed whole W-SDF and those displaying only DSBs in DNA. Two patient cohorts were established: W-SDF ≤30% (low SDF; n = 153) and W-SDF ≥30% (high SDF; n = 222).

Results: An increasing level of W-SDF is associated with an increased incidence of DSBs in the ejaculate. When data from both the low and high W-SDF groups were combined, a linear relationship was observed, with DSBs increasing by 0.799 units for each unit increase in W-SDF. However, when the cohorts were analyzed separately, the relationships differed. In the low SDF group, DSBs increased linearly by 0.559 units for each unit increase in W-SDF. In the high SDF group, DSBs increased exponentially by 0.602 units per unit of W-SDF. Furthermore, the data dispersion between the two variables was significantly different between the cohorts, with the high SDF group showing 0.8 times greater variability than the low SDF group.

Conclusions: While the presence of DSBs in sperm is correlated with the W-SDF present in raw semen samples, the biological mechanisms responsible for DSBs are expressed in different proportions and/or at different levels in ejaculates with higher levels of DNA damage.