The role of reactive oxygen species (ROS) in the pathophysiology of human sperm function has been emphasized in recent years. ROS production in semen has been associated with loss of sperm motility, decreased capacity for sperm-oocyte fusion and loss of fertility. There is a current presumption that the most prolific source of ROS in sperm suspensions is an NADPH oxidase located in leukocytes or in spermatozoa which produces superoxide which is further converted to peroxide by the action of superoxide dismutase. Hydrogen peroxide has been recognized as the most toxic oxidizing species for human spermatozoa, which are very sensitive to lipid peroxidation owing to the high content of polyunsaturated fatty acids in their plasma membrane, though this is not the sole mechanism by which sperm function might be impaired by ROS. Although the excessive production of ROS is detrimental to human spermatozoa, there is a growing body of evidence which suggests that ROS are also involved in the physiological control of some sperm functions. This review focuses on the nature and source of the ROS generated by human spermataozoa as well as their operational mechanisms and their effects, which may be detrimental or beneficial.

The reactive oxygen species, hydrogen peroxide (H2O2) and superoxide anion (O2o-), were generated with a xanthine-xanthine oxidase system and their effect on human sperm function was studied. The action of reactive oxygen species on selected human spermatozoa resulted in a decreased capacity for ionophore-induced acrosome reaction, a decrease in sperm motility, an increase in the concentration of lipid hydroperoxides and a loss of membrane polyunsaturated fatty acids. H2O2 was the key intermediate of the deleterious effects exerted by the xanthine and xanthine oxidase. Among these parameters, the acrosome reaction appeared most susceptible to the reactive oxygen species generated by the xanthine-xanthine oxidase system, and was decreased without sperm motility being affected. Treatment with H2O2 was shown to inactivate several enzymatic activities involved in the antioxidant defence of spermatozoa: glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase. H2O2 and O2o- were shown to be involved in the lipid alterations triggered by the xanthine-xanthine oxidase system. Singlet oxygen is proposed to intervene in the lipoperoxidation process. The inefficacy of mannitol in protecting spermatozoa suggests that hydroxyl radicals were not produced in the extracellular medium.

A complex process of maturation called capacitation is an essential step for spermatozoa to fertilize oocytes. Recent studies have shown that reactive oxygen species (ROS) can enhance the capacitation of human spermatozoa and sperm-zona interaction. We have investigated whether hydrogen peroxide (H2O2) could trigger capacitation of human spermatozoa and the acrosome reaction. The addition of catalase, a specific H2O2 scavenger, at the beginning of the capacitation process decreased the levels of both hyperactivation and induced-acrosome reaction whereas catalase added 15 min before the induction of the acrosome reaction by the calcium ionophore had no effect. Supplementation of the medium with H2O2 resulted in increased levels of hyperactivation and the acrosome reaction, whereas H2O2 added 15 min before induction of the acrosome reaction did not have any stimulatory effect. These results suggest that H2O2 may be involved in the capacitation process of human spermatozoa but not in the acrosome reaction.

Testicular cancer (TC) risk factors remain largely unknown, except for personal history of cryptorchidism and familial history of TC. We conducted a hospital-based case-control study on familial, environmental and occupational conditions in which we compared 229 cases and 800 controls. TC was correlated with cryptorchidism (OR = 3.02; CI: 1.90-4.79), a history of cryptorchidism in relatives (OR = 2.85; CI: 1.70-4.79), and TC (OR = 9.58; CI: 4.01-22.88], prostate cancer (OR = 1.80; CI: 1.08-3.02) and breast cancer (OR = 1.77; CI: 1.20-2.60) in relatives. Living in a rural area or having regular gardening activity (growing fruit or vegetables) was associated with an increased risk of TC (OR = 1.63; CI: 1.16-2.29; OR = 1.84; CI: 1.23-2.75). Regarding occupation, we found a relationship with employment in metal trimming (OR = 1.96; CI: 1.00-3.86), chemical manufacture (OR = 1.88; CI: 1.14-3.10), industrial production of glue (OR = 2.21; CI: 1.15-4.25), and welding (OR = 2.84; CI: 1.51-5.35). In a multivariate model, only a history of cryptorchidism in the men, cryptorchidism in relatives, TC, and breast cancer remained significant. Our findings contribute further evidence to a pattern of TC risk factors, which include the significant weight of personal reproductive history and also of testicular and breast cancer in relatives. By including in a multivariate model variables linked to environmental and occupational exposure and related to familial cancer history, neither living in a rural area nor any occupational exposure appeared to be a potential environmental TC risk factor.

No abstract