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

DNA damage in human spermatozoa is a conundrum. We do not know where it is induced, why it is induced, how it is induced, how to measure it or what it means for fertility or for the health and wellbeing of the offspring. The paper by Agarwal et al. (1) represents an extremely comprehensive capture of our current understanding with respect to measurement methodologies, clinical association and diagnostic implications. However, it is inevitably impacted by our lack of understanding concerning the etiology of DNA damage and the manner in which such damage is ultimately processed by the oocyte and early embryo. Moreover, the key relationship between DNA damage in human spermatozoa and the mutational/epimutational load subsequently carried by the offspring is still a matter for conjecture. We do know that as men age, the spontaneous mutation rate in their children increases in a linear fashion (2) presumably as a consequence of age-dependent damage to the DNA in their spermatozoa. If we can demonstrate that DNA damage in the male germ line is associated with genetic or epigenetic changes in the progeny then we shall have gone a long way towards making the case for conducting routine assessments of DNA damage in spermatozoa, as recommended in Agarwal’s article (1)