Systemic oxidative stress results in oxidative damage to the nucleic acid base most prone to oxidation, guanine, which is then excreted through the urine in the form of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-OHdG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). As a result, seminal plasma will also contain oxidised guanine from the genitourinary tract. Human spermatozoa have been found to be particularly vulnerable to oxidative stress. The subsequent oxidative damage has been commonly identified in the aetiology of male idiopathic infertility.  Additionally, a variety of adverse clinical outcomes affecting both reproductive efficiency and the health and wellbeing of the offspring, are associated with oxidative damage to DNA in spermatozoa.

In this study, we aim to determine if the presence of RNA-base adduct (8-oxoGuo) in the seminal plasma is a good biomarker of systemic oxidative stress and to resolve the degree to which systemic oxidative stress contributes to the oxidation of intracellular DNA in spermatozoa.  Using methods to simultaneously assess intracellular DNA-base adduct formation (8OHdG) in spermatozoa as well as 8OHdG and 8-oxoGuo presence in the corresponding seminal plasma sample; a cohort of 50 assisted conception patients was examined. Pearson correlation analysis was then used to examine the relationship between the data and to determine if patients exhibiting abnormally high levels of intracellular oxidative damage also exhibit high levels of 8-oxoGuo in the seminal plasma.

From preliminary data, we found that, in this cohort, the levels of oxidized RNA in the seminal plasma were not correlated with the degree of intracellular 8OHdG formation. We are currently optimizing the measurement of 8OHdG in seminal plasma. These measurements will then be analysed for correlation with both the intracellular 8OHdG and the 8-oxoGuo in seminal plasma.

If correlated, the optimization of thresholds of 8OHdG in seminal plasma may assist in the diagnosis of systemic oxidative stress and associated oxidative DNA damage in human spermatozoa and, consequently, should assist in the clinical management of male infertility.