Related Experiment Videos
Sperm DNA damage and cancer treatment
1School of Biological Sciences, University of Manchester, Manchester, UK. i.morris@man.ac.uk
Abstract:
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.
Insights
Cancer therapies can harm male fertility and sperm DNA integrity. DNA damage in sperm, assessed by Comet and Chromatin Structure Assay (SCSA), may persist after treatment, posing reproductive risks.
Area of Science:
- Reproductive biology
- Genetics
- Oncology
Background:
- Cancer treatments like chemotherapy and radiotherapy can impair male fertility.
- These treatments can cause DNA damage in sperm, potentially leading to transgenerational effects.
- Assessing sperm DNA damage is crucial for understanding reproductive risks in cancer survivors.
Purpose of the Study:
- To evaluate the impact of cancer treatments on sperm DNA integrity.
- To assess the utility of DNA damage assays in sperm for evaluating reproductive hazards.
- To investigate the persistence and implications of sperm DNA damage post-treatment.
Main Methods:
- Utilized the Comet assay and Chromatin Structure Assay (SCSA) to measure DNA damage in sperm.
- Applied DNA damage assessment methodologies to sperm samples.
- Analyzed sperm DNA integrity in men undergoing or having undergone cancer treatment.
Main Results:
- Both Comet and SCSA assays indicated sperm DNA damage in fertile and infertile men, with some association with infertility.
- Sperm DNA damage was detected after in vivo exposure to genotoxic agents.
- Increased and persistent sperm DNA damage was observed in a patient treated with chemotherapy, consistent with mutagenic effects.
Conclusions:
- Sperm DNA damage assays can directly assess reproductive hazards associated with genotoxic cancer therapies.
- While direct links to offspring genetic disease are not yet established, the potential risk warrants consideration.
- Enhanced surveillance of genetic diseases in offspring of cancer survivors treated with cytotoxic therapies is recommended for accurate risk assessment.