Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa

Reactive oxygen metabolites are known to disrupt sperm-oo-cyte fusion, sperm movement, and DNA integrity; however, the relative sensitivities of these elements to oxidative stress are un-known. In this study these factors were assessed in human sper-matozoa exposed to increasing levels of oxidative stress achieved through the stimulation of endogenous oxidant gen-eration with NADPH or direct exposure to hydrogen peroxide. At low levels of oxidative stress, DNA fragmentation was signif-icantly reduced while the rates of sperm-oocyte fusion were sig-nificantly 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 oxi-dative 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 em-phasize how redox mechanisms can either enhance or disrupt the functional and genomic integrity of human spermatozoa de-pending 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 oo-cyte. These results may have long-term implications for the safe-ty of assisted conception procedures in cases associated with oxidative stress