Background
Oxidative stress (OS) is a recognised pathological process with a well-established link to infertility. Because of this association, antioxidant supplementation is being considered as a therapeutic measure in vivo and in vitro. However, neither the conditions that might support such an intervention nor the optimal reagents to be used in this context, have been adequately undefined. To approach this issue, we have assessed the potential use of amino acids as natural, safe, effective antioxidant supplements for human spermatozoa.
Methods
The antioxidant activity of 22 amino acids was systematically profiled using the RoXsta suite of assays, measuring free radical-, hydrogen peroxide- and lipid peroxide-scavenging activity, respectively. The biological impact of amino acid supplementation on sperm function in culture was then determined for all compounds on 78 normozoospermic semen samples. Shortlisted contenders were trialled as culture medium supplements using DNA integrity, motility and tyrosine phosphorylation as endpoints. Finally, spermatozoa were subjected to oxidative stress induced using hematin, to determine the potential benefits of amino acid supplementation when redox equilibrium is challenged.
Results
Of the 22 amino acids tested, only 4, cysteine, hypotaurine, tryptophan and tyrosine, were revealed to have antioxidant activity. Further investigations showed that cysteine was the sole antioxidant to have a dose-dependent effect on spermatozoa. However, with populations of normal spermatozoa that were not oxidatively stressed, the impact of cysteine on sperm motility, tyrosine phosphorylation and DNA integrity was entirely negative. By contrast, when oxidative stress was simulated using hematin, the antioxidant properties of this molecule were found to significantly improve all aspects of sperm function.
Conclusion
These studies have revealed the potential importance of cysteine as an IVF medium supplement. However, they also highlight that any benefits associated with this compound, are entirely dependent on the redox status state of the cells at the time of exposure.