A Novel Method for Assessing Sublethal Genetic Damage in Sperm

DNA damage in sperm has been linked to infertility and poor reproductive outcomes, however existing methods of sperm DNA analysis have significant limitations and lack the sensitivity to accurately assess sublethal single strand (ss) DNA damage. SsDNA damage is the most prevalent form of DNA damage and of particular concern in sperm because of the implication for transferred genetic damage to future generations.

 In preliminary studies we have developed a novel method for detection and quantification of ssDNA damage called Single Molecule Imaging (SMI). We have successfully adapted SMI for quantification of ssDNA damage in oocytes and have begun adapting the assay for use in human sperm. 

In this project we will continue to optimize the SMI assay for sperm and use this novel method to establish a normal range of DNA damage in human sperm, measure DNA damage levels in sperm in subfertile human patient populations, and investigate the impact of high levels of DNA damage in sperm on fertility and early embryo development using mouse models.

This project aims to develop a new simple, sensitive and robust assay for quantification of ssDNA damage in sperm as both a diagnostic and prognostic test, providing an important parameter by which to assess fertility, improve reproductive outcomes and the safety of ART in at risk patients, and as a tool for toxicology studies

In the future this assay could be developed into:

• A routine sperm analysis test for patients experiencing fertility issues. There are an estimated 50 million infertile couples in the world, 40% of which are caused by male factor.
• A test for comparison of sperm samples to enable selection of optimally healthy sperm for reproduction; for example, sperm cryopreserved for cancer patients prior to treatment compared to sperm produced fresh following cancer treatment. There are approximately 16 million male cancer survivors worldwide.
• A tool for assessing toxicity of new drugs or treatments on sperm genetic integrity