Sperm DNA damage, which negatively affects both natural and assisted fertility, is associated with putative mechanisms such as oxidative stress and defective sperm chromatin packaging. Infertility caused due to oxidative stress-induced sperm damage is mainly through the initiation of apoptosis or the direct oxidation of the DNA by reactive oxygen species (ROS). A recent study published in Reproductive BioMedicine Online highlights the potential of oral antioxidant therapy in substantially improving the sperm DNA integrity and protamine packaging, apart from reducing apoptosis and seminal ROS production in infertile men.
Ozlem Tunc from the Discipline of Obstetrics and Gynaecology, University of Adelaide, South Australia, and coworkers, conducted the study on 50 infertile men with known oxidative stress, to determine the effect of an oral antioxidant or mineral supplement on sperm DNA integrity. The oral antioxidant therapy was administered for 3 months to all the participants, and evaluated, both before and after the treatment, for the following: sperm DNA integrity with terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling, protamination with chromomycin A3, apoptosis with annexin V, and ROS production with nitro blue tetrazolium assay. The researchers also examined serum male reproductive hormones (testosterone, luteinizing hormone, follicle stimulating hormone, and anti-Müllerian hormone), along with sperm parameters such as concentration, morphology, and motility.
The study results showed that the sperm DNA integrity (P=0.002) and protamine packaging (P<0.001) were significantly improved, in addition to a decreased production of ROS (P=0.027) and apoptosis (P=0.004) with the oral administration of antioxidants. However, the scientists did not find any alterations in the levels of the male reproductive hormones and routine sperm parameters.
Earlier, Greco et al. (Journal of Andrology, 2005) conducted a study to determine whether the oral administration of the antioxidants, vitamins C and E reduces the incidence of DNA fragmentation, pathologically enhanced in ejaculated spermatozoa. The study involved 64 patients with unexplained infertility and a raised percentage (≥15%) of sperms with fragmented DNA. The subjects were randomly divided into two subsets: the antioxidant treatment group, wherein the participants received daily doses of 1 g each of vitamins C and E for 2 months, and the placebo group. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay was used to assess the DNA fragmentation both prior to and following the treatment.
Although the researchers did not find any differences in the routine sperm parameters between the two groups, the percentage of sperms with fragmented DNA were markedly lowered (P<0.001) in the antioxidant group following the treatment (9.1 ± 7.2), as opposed to pre-treatment (22.1 ± 7.7). However, the incidence of sperm DNA fragmentation, both pre- and post-treatment, did not vary in the placebo group. Based on the findings, it was suggested that the administration of oral antioxidants for a relatively short period of time could efficiently treat sperm DNA damage.
There exist contradictory results with respect to the role of antioxidants in improving male fertility. In a more recent study, Ménézo (Reproductive Biomedicine Online, 2007) reported that though treatment with the antioxidants, zinc and selenium reduced the sperm DNA fragmentation, it also resulted in an increase in sperm decondensation, which was an unanticipated adverse effect. This was attributed to the unlocking of the interchain disulphide bridges in protamines, which could interfere with the activity of the paternal gene during preimplantation development.
A recent report from the Practice Committee of the American Society for Reproductive Medicine (Fertility and Sterility, 2008) suggested that although the antioxidant supplementation reduces the sperm DNA damage, no definitive effect has been observed on the routine sperm parameters and reproductive outcomes. The report also concluded that there lacks sufficient evidence to support the use of any treatment for abnormal sperm DNA integrity.
References
1. Tunc O, Thompson J, Tremellen K. Improvement in sperm DNA quality using an oral antioxidant therapy. Reprod Biomed Online. 2009 June;18(6). [Epub ahead of print]
2. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005 May-Jun;26(3):349-53.
3. Ménézo YJ, Hazout A, Panteix G, et al. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online. 2007 Apr;14(4):418-21.
4. Practice Committee of American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing. Fertil Steril. 2008 Nov;90(5 Suppl):S178-80.
