Abstract
Human sperm DNA damage may have adverse effects on reproductive outcome. Infertile men possess substantially more spermatozoa with damaged DNA compared to fertile donors. Although the extent of this abnormality is closely related to sperm function, the underlying etiology of ensuing male infertility is still largely controversial. Both intra-testicular and post-testicular events have been postulated and different mechanisms have been proposed to explain the presence of damaged DNA in human spermatozoa. Three among them, i.e. abnormal chromatin packaging, oxidative stress and apoptosis, are the most studied and discussed in the present review. Furthermore, results from numerous investigations are presented, including our own findings on these pathological conditions, as well as the techniques applied for their evaluation. The crucial points of each methodology on the successful detection of DNA damage and their validity on the appraisal of infertile patients are also discussed. Along with the conventional parameters examined in the standard semen analysis, evaluation of damaged sperm DNA seems to complement the investigation of factors affecting male fertility and may prove an efficient diagnostic tool in the prediction of pregnancy outcome.
Highlights
Sperm chromatin maturity and DNA integrity are necessary prerequisites for the completion of fertilization and subsequent embryo development [1]
Taking into account all these data, the present review examines abnormal chromatin packaging, oxidative stress and poor sperm DNA integrity as the possible causes of male infertility
Analysing the impact of specific biomarkers of protaminosis and sperm DNA integrity, it becomes apparent that their use as indicators associated with normal chromatin packaging and normal semen parameters can assist in eliminating the risk of using spermatozoa with defective DNA and, lead to the improvement of male fertility, successful conception and pregnancy outcome
Summary
Sperm chromatin maturity and DNA integrity are necessary prerequisites for the completion of fertilization and subsequent embryo development [1]. Infertile men with varicocele compared to normal controls which had initiated a natural pregnancy, showed statistically significant higher levels of spermatozoal DNA damage, due to high levels of ROS and elevated intratesticular temperature [96] They showed a higher DFI (calculated by the sperm chromatin structure assay-SCSA) and a significant increase of ROS (evaluated by chemiluminescence), in contrast to the lower total antioxidant capacity (TAC) (assessed by enhanced chemiluminescence) [95]. Several studies have demonstrated an age-related increase in sperm cells with double-stranded DNA breaks or poor chromatin packaging [91,109,112-114] This age-related effect may happen as older men produce more sperm with fragmented DNA due to a higher exposure to oxidative stress in their reproductive tracts [32,115]. No statistically significant association between high DFI and early pregnancy loss was observed, contrasting previous reports that reported an increased risk of embryonic loss in pregnancies achieved by the use of semen samples with high rates of DNA breaks [121,123], the possibility that DFI levels higher than 60% might be associated with an increased risk of early pregnancy loss could not be excluded
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