Stimulation of mitochondrial reactive oxygen species production by unesterified, unsaturated fatty acids in defective human spermatozoa.
Male infertility is a relatively common condition affecting 1 in 20 men of reproductive age. The etiology of this condition is thought to involve the excessive generation of reactive oxygen species by human spermatozoa; however, the cause of this aberrant activity is unknown. In this study we demonstrate that defective human sperm populations are characterized by high cellular contents of both esterified and unesterified fatty acids and a decrease in the proportion of the total fatty acid pool made up by docosahexaenoic acid. The free unsaturated fatty acid content of these cells was positively correlated with the induction of mitochondrial superoxide generation (P<0.001). This relationship was causal and mediated by the range of unesterified, unsaturated fatty acids that are present in human spermatozoa. Thus direct exposure of these cells to free unsaturated fatty acids stimulated mitochondrial superoxide generation and precipitated a loss of motility and an increase in oxidative DNA damage, two key attributes of male infertility. We conclude that defective human spermatozoa are characterized by an abnormally high content of fatty acids that, in their unesterified, unsaturated form, promote ROS generation by sperm mitochondria, creating a state of oxidative stress and a concomitant loss of functional competence.
Koppers
Adam J
AJ
Discipline of Biological Sciences and ARC Centre of Excellence in Biotechnology and Development, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia.
Garg
Manohar L
ML
Aitken
Robert J
RJ
D004249:DNA Damage; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013094:Spermatozoa / Q000737:chemistry / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D017382:Reactive Oxygen Species