Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect

Abstract

Reactive oxygen species (ROS) have a negative impact on sperm DNA, leading to the formation of oxidative products such as 8-oxo-7,8-dihydroxyguanosine. This compound causes fragmentation and, thus, has a mutagenic effect. Patient treatment with oral antioxidant vitamins is, therefore, standard practice for male infertility, in an attempt to decrease formation of ROS and improve fertility. In this study, the DNA fragmentation index and the degree of sperm decondensation were measured using the sperm chromatin structure assay before and after 90 days treatment with antioxidant vitamins associated with zinc and selenium. Antioxidant treatment led to a decrease in sperm DNA fragmentation (-19.1%, P < 0.0004), suggesting that at least part of the decay was linked to ROS. However, it also led to an unexpected negative effect: an increase in sperm decondensation with the same order of magnitude (+22.8%, P < 0.0009). The opening of interchain disulphide bridges in protamines may explain this aspect, as antioxidant vitamins, especially vitamin C, are able to open the cystin net, thus interfering with paternal gene activity during preimplantation development. This observation might explain the discrepancy observed concerning the role of these antioxidant treatments in improving male fertility.

Sperm DNA Fragmentation Assays Correlate with Sperm Abnormal Morphology and the Pregnancy Outcome

“…In absence of recognized standard values, some reports established that a normal semen sample generally contains less than 25% stained spermatozoa [37,38] and more recent clinical observations identified threshold values from 28 to over 30%, since no pregnancies were reported following in vitro fertilization and ICSI with semen samples exceeding this percentage [3,24,39,40] In this study we did not find any correlation between SDI and DFI. This lack of correlation has been also shown by other authors [41,42] suggesting that the two kinds of DNA damage are generated by different etiological pathways leading to abnormal chromatin packaging during sperm maturation process for SDI and to an increased sensitivity to oxidative stress and/or apoptosis for DFI [2,43].…”

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

“…This would further help to direct the case specific treatment which could be given to infertile men. There are varied reports [116][117][118] on the efficiency of various antioxidant therapy in infertile men. Recent meta analysis [119,120] of these studies suggest that antioxidant therapy is beneficial and improves various indices of male fertility.…”

Apoptosis and DNA damage in human spermatozoa

“…68 If oxidative stress is at the heart of this process, then antioxidants should surely be part of the cure. Surprisingly, despite an awareness of the importance of antioxidant vitamins to male infertility that stretches back to the 1930s, 69 there have been very few rigorous attempts to evaluate the benefits, and potential risks, 70 of antioxidant therapy in the treatment of male infertility. Studies that have been conducted in this regard have returned generally positive results, 32,[71][72][73] but there is a desperate need for randomized, doubleblind, crossover trials in this area using patients who have been selected with a robust marker of oxidative stress such as 8OHdG.…”