Should we be measuring DNA damage in human spermatozoa? New light on an old question

Abstract

Assessments of sperm DNA damage are controversial because of perceived uncertainties over the relationship with pregnancy and the limited range of therapies available should positive results be returned. In this article, we highlight recent data supporting a chain of associations between oxidative stress in the male germ line, DNA damage in spermatozoa, defective DNA repair in the oocyte, the mutational load carried by the resulting embryo and the long-term health trajectory of the offspring. Any condition capable of generating oxidative damage in spermatozoa (age, obesity, smoking, prolonged abstinence, varicocele, chemical exposures, radiation etc.) is capable of influencing offspring health in this manner, creating a range of pathologies in the progeny including neuropsychiatric disorders and cancer. If sperm DNA damage is detected, there are several therapeutic interventions that can be introduced to improve DNA quality prior to the use of these cells in ART. We therefore argue that infertility specialists should be engaged in the diagnosis and remediation of sperm DNA damage as a matter of best practice, in order to minimize the risk of adverse health outcomes in children conceived using ART.