ABSTRACT
BACKGROUND: Previous reports on effect of antioxidants on sperm DNA integrity were equivocal, and there is a lack of randomized, placebo-controlled studies. OBJECTIVES: To evaluate the efficacy of combined antioxidant treatment in subfertile men with normal reproductive hormone levels and high sperm DNA fragmentation index (DFI). MATERIALS AND METHODS: This placebo-controlled, double-blind, randomized study evaluated the effects of combined antioxidant treatment in 77 men from infertile couples, with normal testosterone, LH and FSH levels and DFI ≥25%. All participants were randomly assigned to receive combined antioxidant treatment (vitamins, antioxidants and oligoelements) or placebo for six months. The primary outcome measured was DFI. Secondary outcomes were standard semen parameters. DFI and other semen parameters were, at each time point (pre-treatment, and after three and six months of treatment), compared between the treatment and the placebo group using Mann-Whitney U-test. RESULTS: Antioxidant group had higher sperm concentration after three months of treatment (median: 24.4 × 106 /mL vs. 27.2 × 106 /mL; P = 0.028) and borderline statistically significant higher concentration after six months of treatment (median: 24.4 × 106 /mL vs. 33.3 × 106 /mL; P = 0.053) compared to pre-treatment values. The DFI did not change during the 6 months of antioxidant therapy. No statistically significant difference between the antioxidant and placebo group was seen for any of the semen parameters including sperm DFI at any of the three time points. DISCUSSION: The increase in sperm concentration was more pronounced in the antioxidant treated group but not statistically significantly higher than among controls, perhaps due to insufficient statistical power. Previous studies have shown positive effect of antioxidant treatment on DFI and other semen parameters. However, our findings indicate that men with normal reproductive hormone levels may not be the primary target group for such therapy. CONCLUSION: Six months treatment with antioxidants had no effect on sperm DFI.
Subject(s)
Antioxidants/therapeutic use , DNA Fragmentation/drug effects , Fertility Agents/therapeutic use , Fertility/drug effects , Infertility, Male/drug therapy , Oxidative Stress/drug effects , Spermatozoa/drug effects , Adolescent , Adult , Antioxidants/adverse effects , Double-Blind Method , Drug Combinations , Fertility Agents/adverse effects , Humans , Infertility, Male/genetics , Infertility, Male/pathology , Infertility, Male/physiopathology , Male , Middle Aged , Sperm Count , Sperm Motility , Spermatozoa/metabolism , Spermatozoa/pathology , Time Factors , Treatment Outcome , Young AdultABSTRACT
The N-methyl-D-aspartate (NMDA) receptors are glutamate-regulated ion channels that are critically involved in important physiological and pathological functions of the mammalian central nervous system. We have identified and characterized the gene encoding the human NMDA receptor subunit NR3A (GRIN3A), as well as the gene (GRIN3B) encoding an entirely novel subunit that we named NR3B, as it is most closely related to NR3A (57.4% identity). GRIN3A localizes to chromosome 9q34, in the region 13-34, and consists of nine coding exons. The deduced protein contains 1115 amino acids and shows 92.7% identity to rat NR3A. GRIN3B localizes to chromosome 19p13.3 and contains, as does the mouse NR3B gene (Grin3b), eight coding exons. The deduced proteins of human and mouse NR3B contain 901 and 900 amino acid residues, respectively (81.6% identity). In situ hybridization shows a widespread distribution of Grin3b mRNA in the brain of the adult rat.
