Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa.
Reactive oxygen metabolites are known to disrupt sperm-oocyte fusion, sperm movement, and DNA integrity; however, the relative sensitivities of these elements to oxidative stress are unknown. In this study these factors were assessed in human spermatozoa exposed to increasing levels of oxidative stress achieved through the stimulation of endogenous oxidant generation with NADPH or direct exposure to hydrogen peroxide. At low levels of oxidative stress, DNA fragmentation was significantly reduced while the rates of sperm-oocyte fusion were significantly enhanced. As the level of oxidative stress increased, the spermatozoa exhibited significantly elevated levels of DNA damage (p < 0.001) and yet continued to express an enhanced capacity for sperm-oocyte fusion. At the highest levels of oxidative stress, extremely high rates of DNA fragmentation were observed but the spermatozoa exhibited a parallel loss in their capacities for movement and oocyte fusion. These studies emphasize how redox mechanisms can either enhance or disrupt the functional and genomic integrity of human spermatozoa depending on the intensity of the oxidative stimulus. Because these qualities are affected at different rates, spermatozoa exhibiting significant DNA damage are still capable of fertilizing the oocyte. These results may have long-term implications for the safety of assisted conception procedures in cases associated with oxidative stress.
MRC Reproductive Biology Unit, Edinburgh EH3 9EW, United Kingdom. r.j.aitken@ed-rbu.mrc.ac.uk
R J
RJ
Aitken
E
E
Gordon
D
D
Harkiss
J P
JP
Twigg
P
P
Milne
Z
Z
Jennings
D S
DS
Irvine
D004247:DNA / Q000032:analysis*; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009249:NADP / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012044:Regression Analysis; D013081:Sperm Motility; D013084:Sperm-Ovum Interactions; D013094:Spermatozoa / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*
D017382:Reactive Oxygen Species; D009249:NADP; D004247:DNA; D006861:Hydrogen Peroxide