Sperm DNA damage and cancer treatment1

Cancer treatments are well known to adversely affect male fertility. Reduction of sperm output arises from the cytotoxic effects of chemo- or radiotherapy upon the spermatogenic epithelium. However, if the epithelium survives there is a hazard to reproduction as the treatments are also mutagenic. The presence of DNA damage in the male genome is shown in animal experiments where there is transgenerational expression as a variety of effects ranging from miscarriage to carcinogenesis. The application of DNA damage methodology to sperm provides the opportunity for direct assessment. The Comet and Chromatin structure assays (SCSA) measure DNA damage by different principles, however, conclusions arising from the data are similar. DNA damage is present in sperm from fertile and infertile men and there is some association with infertility. Both assays detect sperm DNA damage after in vivo treatment with genotoxic agents. In a man treated with chemotherapy for cancer there was increased and persistent DNA damage in sperm. This information is consistent with the generation of human genetic diseases after conception with sperm carrying high loads of DNA damage. Whilst studies have not supported any association between paternal cytotoxic cancer therapy and genetic disease in their children, it would be unwise to discount these observations. The institution of better surveillance of genetic disease in the offspring of men surviving cytotoxic therapies may provide more robust risk assessment.