424. Polyunsaturated fatty acids and mitochondrial reactive oxygen species production in human spermatozoa and male infertility

Abstract

Reactive oxygen species (ROS) are traditionally considered detrimental by-products of cellular metabolism. However, ROS have conflicting roles in human spermatozoa, either as a functional mediator of sperm capacitation or generating a state of oxidative stress that is associated with male infertility. Using the probe MitoSOX Red, we have shown that defective human spermatozoa generate mitochondrial ROS in manner that was negatively correlated with motility (R² = 0.8048). Previous research has shown higher levels of polyunsaturated fatty acids (PUFAs) in defective spermatozoa. However, the addition of PUFA to normal human spermatozoa results in increased mitochondrial ROS production (P < 0.001) and lipid peroxidation (P < 0.001) determined by MitoSOX Red and BODIPY C₁₁ assays, as a consequence human spermatozoa also exhibited decreased sperm motility (P < 0.001). Ongoing research is currently evaluating the relationship between cellular levels of PUFAs in human spermatozoa and mitochondrial ROS generation and decreased sperm motility. This research demonstrates that mitochondrial ROS generation in human spermatozoa may have significant consequences for their function and we propose that elevated PUFA content may be a primary cause of increased oxidative stress and therefore male infertility.