DNA damage in human spermatozoa; important contributor to mutagenesis in the offspring

The importance of sperm DNA damage on human reproduction is increasingly be recognized. Chromatin compaction does not only affect fertility but also exert significant implication of the health and wellbeing of the offspring. Two-step hypothesis has been proposed and represents a rational explanation of how sperm DNA damage occurs. Generation of vulnerable spermatozoa as a result of defect during spermatogenesis represents the first stage of sperm DNA damage. It is followed by oxidative attack which may occurs at all stages of sperm production or transportation due to various causes. As a result, reactive oxygen species constitute a major role in the aetiology of sperm DNA damage. Formation of oxidative base adducts such as 8-hydroxy-2’-deoxyguanosine (8OHdG) commonly occurs upon oxidative attack on sperm DNA. The assessment of oxidative base adducts, therefore, represents another measure of sperm DNA damage. 8OHdG assay may have the advantage in better prediction of offspring health since 8OHdG residues are highly mutagenic. The understanding of sperm DNA damage opens a new doorway to unveil the mystery of human reproduction. On the other hand, there are still many unknowns awaiting for further research. One of the missing link is the relationship between sperm DNA damage and the mutational/epimutational load subsequently carried by the offspring. The demonstration of a positive relationship will further expanding the clinical application of sperm DNA testing and may promote routine use of the test in assessment of male infertility.