Beneficial effect of antioxidant therapy on sperm DNA integrity is not associated with a similar effect on sperm chromatin integrity

Cécile Le Saint, Isaac-Jacques Kadoch, François Bissonnette, Julie Choi, Jonathan Zini, Maria San Gabriel, Armand Zini


Background: Sperm DNA damage has been associated with poor reproductive outcomes. While a number of studies have shown that antioxidants may lower sperm DNA fragmentation, little is known about the effect of oral antioxidants on sperm chromatin integrity. The goal was to evaluate the influence of an antioxidant supplement on sperm chromatin and DNA integrity in a cohort of men with idiopathic infertility.
Methods: This is a retrospective study of 17 consecutive infertile men treated with an oral antioxidant supplement between May 2016 and November 2017. Sperm DNA fragmentation and chromatin integrity were examined before and 3 months after initiating treatment. Sperm DNA fragmentation was measured by a flow cytometry-based terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling (TUNEL) assay and the results were expressed as DNA fragmentation index (%DFI). Sperm chromatin integrity was assessed by aniline blue (AB) staining and the results expressed as % chromatin damage.
Results: It was observed that oral antioxidant therapy was associated with a significant decrease in mean [± standard error (SE)] %DFI (38.6%±1.7% to 26.6%±1.8%, P<0.0001), with the majority of patients (94%) experiencing a diminution in their %DFI after therapy. However, antioxidant therapy was not associated with a significant change in chromatin damage (28.8%±3.2% to 30.1%±2.8%, P=0.48).
Conclusions: The data show that infertile men may experience a reduction in sperm DNA fragmentation, but not chromatin integrity after oral antioxidant therapy. This may be explained by the possible interference of antioxidants with the mild oxidative stress (OS) required for induction of sperm chromatin compaction. These data demonstrate the complex nature of sperm chromatin and the variable influence of OS on sperm chromatin targets.