Oxidative stress in the male germ line (#105)
Oxidative stress is a major cause of male infertility that has been studied throughout the years and is a prominent reason as to why couples experiencing male factor infertility are desperately seeking assisted reproductive technologies (ART). This increased in ART is thought to have contributed to a rise in birth defects, morbidity and abnormalities in children conceived compared to naturally conceived children as a result of the elimination of the natural sperm selection mechanisms.
A proposed reason for this is an increase in reactive oxygen species (ROS) which in turn causes an increase in oxidative stress. ROS is necessary within the reproductive system, however in surplus can cause lipid peroxidation and DNA damage. Studies have shown that the ROS responsible for inducing oxidative damage in human spermatozoa are derived from two independent cellular sources, leukocytes and spermatozoa. While oxidative stress is thought to play a significant role in male infertility, the source of the free radicals responsible for this pathology has not been previously explained.
We are currently exploring potential mechanisms within the population of patients attending IVF clinics and a reference cohort of normozoospermic donors. Our data has shown an increase in lipid peroxidation, caspase activation via FLICA and Annexin V binding as well as a rise in 8-oxoguanine adducts. We have also seen an increase in Homocysteine levels in IVF patients, interestingly; these elevated results have been positively correlated with sperm motility but negatively correlated with Folic acid levels, suggesting this unbalance is a another reason for patients seeking IVF treatment. The results of this study will serve as a solid platform for the development of future studies and become a major contribution towards our understanding of the incidence and source of oxidative stress in the patient population and the help shape future studies on the aetiology and management of this condition.