Abstract
Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for 50% of the cases. Currently, a physical examination, hormone profiling and the evaluation of two consecutive semen samples (to determine the sperm concentration, motility, morphology and, in very few cases, sperm DNA integrity) are the sole tools that physicians have to evaluate infertility in men. Antioxidant therapy is often used to improve sperm quality and function in infertile men. However, there are controversial results regarding the efficacy of these treatments. Prdx6−/− male mice are subfertile, displaying significant oxidative damage in the lipids, proteins and DNA of their spermatozoa. Here, we used Prdx6−/− male mice to test whether a novel combination of tocopherols that contained 60% γ-tocopherol and ascorbic acid could restore their fertility. These mice were fed with the supplemented (Vit. Mix) or control diets. To assess sperm quality, we determined the motility, levels of lipid peroxidation, DNA oxidation and tyrosine nitration in the spermatozoa. The number of pups sired by the Prdx6−/− mice fed with the Vit. Mix diet was higher than that sired by the males fed with the control diet, and the pups’ mortality was lower. The sperm quality was improved in the males fed with the supplemented diet. We concluded that treatment with a supplement composed of tocopherols and rich in γ-tocopherol and ascorbic acid is effective in restoring fertility in cases where oxidative stress and high levels of tyrosine nitration are associated with male infertility.
Highlights
Male infertility is of great medical issue in humans because approximately 16% of couples worldwide are affected by infertility, and in 50% of these cases, the causes can be ascribed to the man [1].Environmental pollutants, chemicals, drugs, smoke, toxins, radiation and diseases that have adverse effects on fertility have in common oxidative stress [2,3,4,5,6]
We found that patients with idiopathic infertility had reduced amounts of peroxiredoxin 6 (PRDX6) in spermatozoa compared to healthy donors [11]
We previously demonstrated that fertilization rates were reduced by 80% when using Prdx6−/− compared to wild type (WT) spermatozoa, and Prdx6−/− spermatozoa were unable to produce blastocysts in vitro [17]
Summary
Male infertility is of great medical issue in humans because approximately 16% of couples worldwide are affected by infertility, and in 50% of these cases, the causes can be ascribed to the man [1].Environmental pollutants, chemicals, drugs, smoke, toxins, radiation and diseases that have adverse effects on fertility have in common oxidative stress [2,3,4,5,6]. The presence of high levels of reactive oxygen species (ROS) in semen has been reported in 25–87% of infertile patients [7,8,9]. Male idiopathic infertility has a prevalence of 23% [10]. We found that patients with idiopathic infertility had reduced amounts of peroxiredoxin 6 (PRDX6) in spermatozoa compared to healthy donors [11]. Thiol-oxidized PRDX6 (inactive) levels and the presence of high molecular mass complexes (containing the inactive PRDX6-SO2 ) [12] are present in the spermatozoa in 90% of idiopathic infertile men [11]. Due to the reduced amounts of the PRDX6 protein and its oxidation status, very little
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