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ABSTRACT: Telomeres play a fundamental role in the organization of the sperm nucleus resulting in the looped chromosome configuration and non-random positioning of chromosomes. Telomeres localize in the nuclear periphery and interact dynamically by forming dimers and tetramers. The purpose of this study was to evaluate the relationship of telomere interactions to DNA damage, a factor known to adversely influence male fertility. Telomeres were localized by fluorescence in situ hybridization (FISH) using human chromosome pan-telomeric probe in ten samples with low and ten samples with high sperm DNA damage. The samples with a low DNA fragmentation index (DFI) had a mean number of telomere signals of 21.7±1.9 compared to a mean of 26.5±3.4 signals in the samples with a high DFI (p<.005). The percentage of cells with a typical telomere distribution of ≤23 telomere-telomere dimers was observed in 70.8%±15.6 samples with a low DFI compared to 44.2%±22.4 in samples with a high DFI (p<.05). These results suggest that sperm DNA damage is associated with disruption of the normal telomere-telomere interactions leading to possible loss of the looped chromosome configuration. Improperly packed and organized sperm chromatin might have a high probability of disrupting the extremely structured sequence of sperm chromosome deposition, activation, and processing by the oocyte at the time of fertilization. These results might provide additional information on the nature of sperm DNA damage and the role of such damage on fertilization and development of the zygote.
Systems biology in reproductive medicine 10/2010; 56(6):407-12. · 0.80 Impact Factor
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ABSTRACT: To analyze the relationship between DNA damage and standard semen parameters (SSP) in patients who present for fertility evaluation. Evaluation of male fertility includes assessment of the SSP and increasingly sperm DNA damage. However, the relationship between DNA damage and SSP remains controversial.
Following Institutional Research Ethics Board approval, semen samples from 2586 unselected nonazoospermic patients were subjected to computer-assisted semen analysis and flow cytometry-based sperm DNA damage assessment expressed as the DNA fragmentation index.
Sperm DNA damage was significantly negatively correlated to sperm SSP (concentration, motility, and normal morphology) and positively correlated to patient's age. DNA damage increased in association with the number of abnormalities in SSP. Patients with oligoasthenoteratozoospermia had significantly higher DNA damage and more frequent DNA damage over 30% compared with normozoospermic patients and patients with abnormalities in 1 or 2 SSP.
Our results indicate that DNA damage is significantly correlated to SSP as well as age. In addition, the degree of DNA damage increases with the number of abnormal parameters in a sample and is most severe in patients with oligoasthenoteratozoospermia. Complex and possibly age-related mechanisms of DNA damage in human spermatozoa may be responsible for the strong relationship between SSP and DNA fragmentation index.
Urology 08/2009; 74(4):789-93. · 2.43 Impact Factor
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ABSTRACT: The purpose of our study was to analyze the relationship of leukocytospermia to sperm DNA damage as assessed by the DNA integrity assay. Results indicate that leukocytospermia has a significant negative effect on the standard semen parameters of concentration, motility, and morphology but at most a very weak effect on DNA integrity as measured by the DNA fragmentation assay.
Fertility and sterility 10/2007; 88(3):737-40. · 3.97 Impact Factor
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ABSTRACT: The purpose of this study was to analyze the relationship of male age and DNA integrity in men presenting for investigation of infertility. We found that men 45 years and older had significantly greater DNA fragmentation than younger men.
Fertility and sterility 03/2006; 85(2):496-9. · 3.97 Impact Factor
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ABSTRACT: To examine the retention of sperm cytoplasmic droplets (CD) and DNA denaturation (DD) in semen from fertile and infertile men.
Semen samples were obtained from consecutive nonazoospermic men presenting for infertility evaluation (n = 101) and fertile men presenting for vasectomy (n = 13). The standard semen parameters (sperm concentration, motility, and morphology), sperm DD, and sperm CD were monitored. Sperm DD was evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa demonstrating denatured DNA.
The mean (+/-SE) percentages of spermatozoa with CD and DD were significantly higher in infertile than in fertile men (sperm CD 15.7% +/- 0.8% versus 4.8% +/- 0.7% and sperm DD 22.0% +/- 1.5% versus 10.8% +/- 1.8%, respectively). Sperm CD and DD were positively correlated (r = 0.59). Also, sperm CD and DD values correlated inversely with the standard semen parameters.
Our data demonstrate that the retention of sperm CD correlates positively with sperm DD and that significantly higher sperm DD and CD are found in infertile than in fertile men. These data suggest that the enhanced susceptibility of sperm DNA to denaturation is associated with the abnormal disposal of residual sperm cytoplasm in the testis and/or epididymis.
Urology 02/2003; 61(1):207-11. · 2.43 Impact Factor
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ABSTRACT: The objective of this study was to examine the relationship between DNA integrity and protamines in human sperm. One hundred forty-nine male infertility patients were included in an Institutional Review Board-approved study. Sperm were evaluated for DNA fragmentation using the DNA Integrity Assay, a test equivalent to the sperm chromatin structure assay (SCSA). Additionally, nuclear proteins were extracted and the protamine-1/protamine-2 ratio (P1/P2), protamine-1 (P1), protamine-2 (P2), and total protamine concentrations were evaluated. We identified 37 patients with abnormally low P1/P2 ratios, 99 patients with normal P1/P2 ratios, and 13 patients with abnormally high P1/P2 ratios. DNA fragmentation was significantly elevated in patients with low P1/P2 ratios (37.1 +/- 6.02) vs those with normal and high P1/P2 ratios (26.7 +/- 1.9 and 23.8 +/- 3.2, respectively; P < .05) and was inversely correlated with the P1/P2 ratio (R(s) -0.18, P < .05), P1 concentration (R(s) -0.29, P < .001), P2 concentration (R(s) - 0.24, P < .005), and total protamine concentration (R(s) -0.28, P < .001). Furthermore, chi2 analysis revealed a significant increase in the incidence of marked DNA fragmentation in patients with diminished levels of either P1 or P2. The present study is the first to report that human sperm protamine content is significantly related to DNA fragmentation. In particular, sperm P1 and P2 concentrations inversely correlate with DNA fragmentation, indicating a protective role of the protamines against sperm DNA damage. In light of recent studies highlighting the negative effect of sperm DNA damage on ART outcomes, these findings indicate a possible clinical significance for human sperm protamine levels.
Journal of Andrology 26(6):741-8. · 2.97 Impact Factor
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ABSTRACT: Objectives. To examine sperm DNA denaturation (DD) in fertile and infertile men and assess the variability of conventional semen parameters and sperm DD in repeated semen samples from infertile men.Methods. Twenty-one consecutive nonazoospermic, infertile men each submitted two semen samples, 2 to 6 weeks apart. We examined semen samples from consecutive fertile men (n = 10) presenting for vasectomy as controls. Standard semen parameters (World Health Organization criteria) and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa with denatured DNA) were monitored.Results. Fertile men had a significantly higher sperm concentration and percentage of sperm motility and a significantly lower percentage of sperm with DD than did infertile men (36 ± 5.2 × 106/mL versus 12.5 ± 2.2 × 106/mL, 60.0% ± 5.2% versus 30.1% ± 4.1%, and 8.9% ± 1.9% versus 20.3% ± 2.5%, respectively, P <0.05). The sperm concentration, sperm motility, and percentage of spermatozoa with DD were not significantly different between the first and second semen samples from the infertile men. Sperm DD showed the lowest average within-subject coefficient of variation (SD/mean), followed by motility and concentration (coefficient of variation 21%, 24%, and 35%, respectively).Conclusions. Our data demonstrate that infertile men have significantly higher sperm DD compared with fertile men and that sperm DD exhibits a low coefficient of variation (∼20%) on repeated assessment. These data suggest that sperm DD has a relatively low degree of biologic variability.
Urology.
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ABSTRACT: Assessment of sperm DNA damage has been suggested as a negative predictor of fertility potential. Multiple pathological factors acting at both the intra-testicular and post-testicular levels may contribute to sperm DNA damage. The relative contribution of each of these factors in an individual with high DNA damage (>30%) is unclear. The management of patients with elevated DNA damage is also challenging. The purpose of our retrospective study was to evaluate the clinical course of patients with sperm DNA damage over 30% and to assess the effect of non-specific (oral antioxidant) and cause-specific treatments on the quality of their sperm DNA. Results of our retrospective study suggest that the evaluated group with high DNA damage was diagnostically heterogeneous and comprised patients with varicoceles, bacteriospermia and idiopathic infertility. A three month course of antioxidant therapy reduced sperm DNA damage in only 30/61 (49%) patients with significant improvement between the initial and post-treatment DNA Fragmentation Index (DFI) results (46.8%+/-14.1 vs. 36.7%+/-16.6, p < .001). The positive effect of antioxidants could be age-dependent, as patients older that 40 years of age showed no improvement after such treatment. The cause-specific treatments showed superior results compared to antioxidants alone. Improvement was observed in 7/9 (78%) of patients after surgical varicocele repair between the initial and post-treatment DFI results (44.7%+/-12.8 vs. 28.4%+/-9.5, p < .03). The majority of the patients 13/14 (93%) with bacteriospermia had improvement in sperm DFI results after antibiotic treatment (50.4%+/-19.1 vs. 38.6%+/-18.7, p < .001).
Systems biology in reproductive medicine 55(2):109-15. · 0.80 Impact Factor
