Male aging as a causative factor of detrimental changes in human conventional semen parameters and sperm DNA integrity.

The effect of male aging on fertility potential is controversial and difficult to predict. The aim of our study was to determine the associations between age, basic semen parameters, and sperm DNA fragmentation (SDF). Comparison of four age-dependent groups (men ≤29 years, 30-35 years, 36-40 years, and >40 years) revealed a significant fall in the basic semen characteristics and sperm genomic integrity with age. Receiver operating characteristic (ROC) analysis confirmed that men >29 years had lower semen quality. In the group of men >29 years, the prevalence of men with abnormal semen parameters was higher, and these men had over a threefold higher odds ratio (OR) for abnormal semen parameters. Next, ROC analysis revealed that a threshold of 18% SDF was optimal for discriminating between men with normal and abnormal standard semen parameters. The prevalence of men with >18% SDF was higher in the group of men >29 years than in men ≤29 years. Older men had an almost twofold higher risk for >18% SDF than younger men. Our results suggest that age >29 years may be a causative factor of detrimental changes in semen quality, which may raise the risk for disorders of male fertility potential.

Evaluation of selected semen parameters and biomarkers of male infertility - preliminary study.

Background: Because the etiopathogenesis of male infertility is multifactorial our study was designed to clarify the relationship between standard semen parameters, testicular volume, levels of reproductive hormones and the fragmentation of sperm nuclear DNA (SDF). Methods: Patients (n = 130) were clustered as subjects: 1) with an abnormal volume (utrasonography) of at least one testis (<12 mL) or with a normal volume of testes and 2) with abnormal levels of at least one of the reproductive hormones (FSH, LH, PRL, TSH, total T - electrochemiluminescence method) or with normal hormonal profiles and 3) with high level of SDF (>30%), moderate (>15-30%) or low (≤15%) (sperm chromatin dispersion test). Results: In subjects with a decreased testicular volume and in subjects with abnormal levels of reproductive hormones, decreased basic semen parameters were found. Participants with abnormal testicular volume had a higher percentage of SDF and a higher level of FSH (Mann-Whitney U test). In turn, men with a high level of SDF had lower testicular volume and conventional sperm parameters than men with a low level of SDF (Kruskal-Wallis test). Conclusions: We showed that spermatogenesis disorders coexisted with decreased testicular volume and increased FSH levels. The disorders of spermatogenesis were manifested by reduced basic sperm characteristics and a high level of sperm nuclear DNA damage.

Relationship between sperm morphology and sperm DNA dispersion.

BACKGROUND: The pathogenesis of teratozoospermia (<4% morphologically normal sperm cells) and the relationship between sperm morphological abnormalities and abnormal sperm nuclear DNA fragmentation, which are considered indicators of male fertility, have not been elucidated. Our research was designed to determine the prevalence of different sperm DNA fragmentation (SDF) levels in men with teratozoospermia and to establish a discriminating threshold value for SDF in assessing sperm morphology. METHODS: Basic semen characteristics and detailed sperm morphological analysis (head, neck, midpiece, and tail defects and excess residual cytoplasm) (WHO, 2010), and the nuclear sperm DNA dispersion test were performed on semen samples obtained from 523 men with teratozoospermia (n=296) and those without teratozoospermia (n=227). RESULTS: Subjects with abnormal sperm morphology had not only lower results for standard sperm characteristics, including detailed sperm morphological abnormalities, but also a higher proportion of sperm cells with SDF vs. men with normal sperm morphology. Moreover, significantly fewer subjects with low SDF levels (≤15%), more subjects with high SDF levels (>30%) and a higher odds ratio (OR) for having high SDF levels were found in the group of men with teratozoospermia vs. men without teratozoospermia. However, the receiving operating characteristic (ROC) curve analysis indicated that a SDF >18% was a significant negative predictive value to distinguish between men with normal sperm morphology or men with abnormal sperm morphology. The optimal area under the ROC curve (AUC) was 0.746. In the group of men with teratozoospermia, a higher incidence of men with >18% SDF and a higher OR for having >18% SDF were observed. SDF negatively correlated with sperm number, morphologically normal sperm cells, sperm motility and sperm vitality but positively correlated with the teratozoospermia index (TZI) and detailed sperm morphological abnormalities. CONCLUSIONS: The obtained findings demonstrated that: (I) detailed sperm structural defects coexist with abnormal nuclear sperm DNA dispersion, (II) men with teratozoospermia may have a higher risk for sperm DNA damage, (III) the calculated optimal SDF value of 18% measured by the DNA sperm dispersion test is the best criterion to predict normal and abnormal sperm morphology.

The higher risk for sperm DNA damage in infertile men.

OBJECTIVES: Supplementary assays are needed for determination of relationships between sperm biomarkers and fertility potential. Therefore, our research was designed to determine the extent of sperm DNA fragmentation (SDF) and establish a discriminating threshold of SDF for fertility potential. MATERIAL AND METHODS: Semen characteristics were evaluated according to World Health Organization recommendations, and SDF was assessed by sperm chromatin dispersion test on ejaculated spermatozoa from infertile and healthy normozoospermic men. RESULTS: A higher proportion of SDF was noted in infertile men (median 23.00%) than normozoospermic (median 14.00%). Significantly less subjects (17.03%) with low SDF level (≤ 15%) and more (35.17%) with high SDF level ( > 30%) were found for the infertile group vs the normooospermic (57.90% and 5.26%, respectively). Infertile group had significantly lower odds ratio (OR) for having a low SDF level (OR: 0.1493) and higher OR for having a high SDF level (OR: 9.7627). Receiver operating characteristic analysis [area under curve (AUC) = 0.785] revealed that 20% SDF is predictive value for discriminating between infertile and normozoospermic subjects. SDF was negatively correlated with the sperm number, morphology, progressive motility and vitality but positively with the teratozoospermia index. CONCLUSIONS: Our study demonstrates: (1) a significant difference in the extent of SDF and in the risk for having damaged sperm DNA between infertile and normozoospermic men, (2) > 20% SDF has negative predictive value for fertility potential, (3) coexistence of abnormal standard sperm parameters with sperm chromatin damages. Therefore, SDF should be considered as a highly valuable indicator of male fertility potential.

Age-related changes in human sperm DNA integrity.

Abnormal standard semen characteristics and reduced sperm chromatin maturity can appear with increasing male age. However, the influence of paternal age on semen parameters is still controversial. Therefore, this study was designed to estimate the influence of paternal age not only on conventional semen characteristics but also on sperm DNA integrity. This research was carried out on ejaculated sperm cells obtained from men (n = 1124) aged ≥40 y and <40 y. Our data revealed a decreased semen volume and an increased percentage of DFI (sperm DNA fragmentation index) in older men compared to younger men in the entire study cohort, in men with normozoospermia and in men with abnormal semen parameters. Moreover, there was a higher incidence of sperm DNA damage (>10% DFI, low fertility potential) in the groups of men aged ≥40 y than in the groups of men aged <40 y. Older men had over twice the odds ratio for high sperm DNA damage as younger men. Our findings suggest a detrimental effect of advanced paternal age on sperm chromatin integrity. The data show that the evaluation of sperm DNA has greater clinical utility than standard semen analysis in case of male fertility potential assessment.

The impact of sedentary work on sperm nuclear DNA integrity.

INTRODUCTION: Contemporary professional jobs that often enforce a sedentary lifestyle and are frequently associated with testicular overheat, deserve special attention with respect to male fertility potential. Interestingly, the harmful effect of testicular heat stress on sperm characteristics including nuclear DNA integrity was well characterized; however, the influence of sedentary work on sperm chromatin has not yet been documented. Therefore, our research was designed to examine the potential effects of sedentary work not only on conventional semen features but also on sperm nuclear DNA status. MATERIALS AND METHODS: The study was carried out on ejaculated sperm cells obtained from men who spent ≥ 50% of their time at work (≥ 17.5 h per week) in a sedentary position (n = 152) and from men who spent < 50% of their time at work in a sedentary position (n = 102). Standard semen characteristics were assessed according to the WHO 2010 recommendations, while sperm nuclear DNA fragmentation (SDF) was evaluated using the Halosperm test. RESULTS: There were no significant differences in the standard semen parameters between the study groups. The groups differed only in SDF parameter. The men who spent at least 50% of their work time in a sedentary position had a higher proportion of SDF than the men who spent < 50% of their time at work in a sedentary position (median value 21.00% vs. 16.50%, respectively). The incidence of low SDF levels (related to 0-15% sperm cells with abnormal DNA dispersion) was significantly lower (27.63% vs. 45.10%), the percentage of men with high SDF levels (related to > 30%) was significantly higher (30.92% vs. 16.67%) in group of men who spent at least 50% of their work time in a sedentary positon. Furthermore, these men were more than twice as likely to have not a low SDF level (OR: 0.4648) and had more than twice the risk of having a high SDF level (OR: 2.2381) than the men in less sedentary occupations. CONCLUSIONS: Despite lack of association between sedentary work and conventional semen characteristics our study revealed detrimental effect of seated work on sperm nuclear DNA integrity. A sedentary job doubled the risk of high levels of sperm DNA damage. The pathomechanism could be related to testicular heat stress resulting in sperm chromatin remodelling failure during spermiogenesis. Therefore, it seems reasonable to simultaneously carry out routine seminological analyses and tests assessing sperm chromatin status while diagnosing male infertility.

Utility and Predictive Value of Human Standard Semen Parameters and Sperm DNA Dispersion for Fertility Potential.

Because the assessment of sperm DNA fragmentation (SDF) plays a key role in male fertility, our study was designed to find the relationships between SDF and standard semen parameters. The receiver operating characteristic (ROC) curve showed that 18% SDF is a prognostic parameter for discriminating between men with normal and abnormal standard semen parameters (n = 667). Men with > 18% SDF had significantly lower quality semen, a higher prevalence of abnormal semen characteristics, and a higher odds ratio for abnormal semen parameters compared to men with ≤ 18% SDF. An ROC analysis provided predictive values for age and semen parameters to distinguish between men with SDF > 18% and men with ≤ 18% SDF. SDF was positively correlated with male age and teratozoospermia index but negatively with sperm concentration, total number of spermatozoa, sperm morphology, progressive motility, and vitality. Our study shows that 18% SDF has a predictive value for distinguishing between men with normal and abnormal semen characteristics. Men with >18% SDF have a higher risk for abnormal semen parameters, while age and obtained semen parameters have a predictive value for SDF. There is a relationship between SDF and conventional sperm characteristics, and thus, SDF can be incorporated into male fertility assessment.