High Sperm DNA Damage Research Articles

Joint Effects of XRCC1 Polymorphisms and Polycyclic Aromatic Hydrocarbons Exposure on Sperm DNA Damage and Male Infertility

X-ray repair cross-complementing group 1 (XRCC1) plays a role in repairing polycyclic aromatic hydrocarbons (PAHs)-induced DNA damage. We examined the effects of exposure to PAHs and XRCC1 polymorphism, alone or combined, on sperm DNA integrity and male fertility. A total of 620 idiopathic infertile subjects and 273 fertile controls were recruited in this study. PAHs exposure was indicated by urinary 1-hydroxypyrene level. Genotypes were determined by PCR-RFLP, and sperm DNA damage was detected by Tdt-mediated dUTP nick end labelling assay using flow cytometry. A positive correlation was found between PAHs exposure and sperm DNA damage (beta coefficients = 0.183, p < 0.001), whereas there was no significant association between the XRCC1 polymorphisms and sperm DNA damage. However, when the patients were dichotomized for PAHs exposure, higher sperm DNA damage was found among 399Gln allele carriers compared with the wild-type homozygotes (p = 0.033). Further analysis based on a case-control study revealed the joint effect of XRCC1-399 polymorphism and PAHs exposure on the risk of male infertility (p interaction = 0.041). These findings provided the first evidence about potential joint effects of PAHs exposure and DNA repair gene polymorphisms on male reproductive system and may be helpful in improving our understanding of the etiology of male infertility.

Frequency and severity of sperm DNA damage in patients with confirmed cases of male infertility of different aetiologies

Men with high sperm DNA damage have a reduced fertility potential. Correlation of specific clinical factors to the degree of sperm DNA damage remains unclear. This retrospective study evaluated the frequency and severity of sperm DNA damage in men with different aetiologies of male factor infertility. Patients with male factor infertility (n=288) underwent flow cytometry-based sperm DNA damage assessment and results were correlated with the major aetiologies of male infertility: varicocele, bacteriospermia and idiopathic infertility. Sperm DNA damage was significantly correlated to the patient's age, sperm motility, normal morphology and vitality (P < 0.001). High sperm DNA damage (30%) was most frequently found in the group with bacteriospermia (48%), compared with 30% of the men with varicoceles and 22% of the men with idiopathic infertility (P < 0.02). While some tendency was observed for a correlation of increasing sperm DNA damage in patients with grade III and bilateral varicoceles, this difference did not reach statistical significance. The data support the importance of proper physical and laboratory investigations of the fertility status in men to correctly diagnose and treat male infertility.

Cause-Specific Treatment in Patients with High Sperm DNA Damage Resulted in Significant DNA Improvement

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).

Sperm DNA damage in men from infertile couples

To investigate the prevalence of high levels of sperm DNA damage among men from infertile couples with both normal and abnormal standard semen parameters. A total of 350 men from infertile couples were assessed. Standard semen analysis and sperm chromatin structure assay (SCSA) were carried out. Ninety-seven men (28% of the whole study group) had a DNA fragmentation index (DFI)> 20%, and 43 men (12%) had a DFI>30%. In the group of men with abnormal semen parameters (n = 224), 35% had a DFI>20%, and 16% had a DFI>30%, whereas these numbers were 15% and 5%, respectively, in the group of men with normal semen parameters (n=126). Men with low sperm motility and abnormal morphology had significantly higher odds ratios (ORs) for having a DFI>20% (4.0 for motility and 1.9 for morphology) and DFI>30% (6.2 for motility and 2.8 for morphology) compared with men with normal sperm motility and morphology. In almost one-third of unselected men from infertile couples, the DFI exceeded the level of 20% above which, according to previous studies, the in vivo fertility is reduced. A significant proportion of men with otherwise normal semen parameters also had high sperm DNA damage levels. Thus, the SCSA test could add to explaining causes of infertility in cases where semen analysis has not shown any deviation from the norm. We also recommend running the SCSA test to choose the appropriate assisted reproductive technique (ART).

Higher Sperm DNA Damage in Semen From Men With Spinal Cord Injuries Compared With Controls

Semen from men with spinal cord injuries (SCI) and control subjects was investigated for sperm DNA damage using the sperm chromatin structure assay. Three experiments were performed. In experiment 1, the DNA fragmentation index (DFI) was compared in semen from SCI subjects and control subjects. In experiment 2, the % DFI was determined in repeated ejaculations to examine the effect of anejaculation on DFI. In experiment 3, the DFI was determined in neat vs processed semen to examine the effect of necrospermia or leukocytospermia on DFI. The results of experiment 1 showed a significantly higher mean (+/- SEM) DFI in the semen of SCI subjects (65.2% +/- 6.6%; range, 42.3%-90.8%) compared with control subjects (15.4% +/- 2.9%; range, 5.4%-33.5%; P < .001). In experiment 2, there was a high correlation between the DFIs obtained in the first semen specimens and the DFIs obtained 3 days later in semen of the same SCI subjects (r(s) = .94; P < .02). In experiment 3, the results showed no significant difference between mean DFI in aliquots of neat semen (79.3% +/- 9.9%) vs matched aliquots of semen processed to remove dead sperm and leukocytes in SCI subjects (75.2% +/- 16.1%). The DFI is higher in semen from men with SCI vs controls. The cause of this condition is unknown but does not seem to be due to prolonged anejaculation or to the proximate conditions of necrospermia or leukocytospermia. The relevance of these findings to fertility outcomes with SCI male partners remains to be determined.

High sperm DNA damage is not associated with sperm penetration assay using zona-free hamster oocytes in a multivariable analysis

High sperm DNA damage has been associated with abnormal semen analysis parameters and poor prognosis for in vitro fertilization (IVF) cycles. Our goal is to evaluate the relationship between sperm penetration assay (SPA) results and sperm DNA damage.

The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development.

The integrity of sperm DNA is important for the success of natural or assisted fertilization, as well as normal development of the embryo, fetus and child. ICSI, by bypassing sperm selection mechanisms, increases the risk of transmitting damaged DNA and the significance of this requires investigation. DNA damage in sperm from an unselected group of 60 men undergoing IVF treatment was measured by single cell gel electrophoresis (Comet assay) and correlated with semen and treatment cycle parameters. Wide spectra of sperm DNA damage were found both within and between men but no specific subgroups were identified. Semen and treatment cycle parameters were not different in men grouped according to high or low sperm DNA damage. However, regression analysis showed that DNA damage was positively associated with age (29-44 years), abnormal sperm and motility and negatively associated with sperm concentration. In ICSI cycles DNA damage was positively associated with impairment of post-fertilization embryo cleavage. This study contributes to the evidence of DNA damage within sperm. High loads of DNA damage measured by the Comet assay were predictive of failure of embryo development after ICSI. As it is likely that sperm with DNA damage contributed to successful fertilization and in-vitro development, potential adverse effects remain to be clarified.