ANDROLOGIA 29, zyxwvutsrqp 125- 13 1 (1 997) ACCEPTED: AUGUST 14, 1996 Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility? T. Oeda'.', R. Henkel', H. Ohmori' and W.-B. Schill' 'Center of Dermatology and Andrology, Justus Liebig University, Giessen, Germany; *Department of Urology, Okayama University Medical School, Okayama,Japan Key words. N-acetyl-L-cysteine-reactive oxygen species-human semen-male infertility zyxw Summary. A new approach to reduce the level of reactive oxygen species (ROS) in human semen by using N-acetyl-L-cysteine (NAC) was evaluated. Semen samples were incubated with or without NAC (1.0 mgml-') at room temperature. The chemiluminescent signal of the oxidation of lumi- no1 was detected by means of an MTP reader after 0, 20, 40, 60 and 120 min, respectively, using 200 pM luminol. In addition, the dose-dependent action of NAC (0.1, 1.0 and 5.0 mg ml-') and the influence of NAC on functional sperm parameters (motility and acrosome reaction) were studied. ROS levels decreased significantly after 20 min incubation with NAC. This reduction was greater in the high ROS group (>30000 counts/107 viable sperm at t zyxwvutsr = 0) than in the low ROS group (<30000). In addition, a marked dose- dependence of NAC was observed. Concerning sperm function, total sperm motility improved after incubation with NAC, but no significant change was observed with respect to the acrosome reaction. NAC (at concentrations of 1 .O mg ml- ') signifi- cantly reduced ROS in human semen and showed the possibility of improving impaired sperm func- tion. After further testing NAC might be useful for the treatment of male infertility patients. Introduction Although loss of sperm function is thought to be a major problem for infertile couples because of low fertilization rates (Shushan zyxwvutsr et al., 1995), the Correspondence: Dr R. Henkel, Center of Dermatology and Andrology, Justus Liebig University, Gaffkystr. 14, D-35385 Giessen, Germany. true aetiological factor of this complicated patho- logical condition is still uncertain. Many studies have been performed focusing on the treatment of idiopathic male factor infertility, but a truly effec- tive therapeutic procedure is not readily available (O'Donovan et al., 1993). In several studies, reactive oxygen species (ROS), such as hydrogen peroxide (H202), super- oxide anion (Oz-) and/or hydroxyl radical (.OH), have been suggested to be essential factors of impaired sperm function (Aitken et al., 1989; Mortimer, 1991; Ochsendorf et al., 1994).Whereas ROS mainly originate from neutrophile granulo- cytes in semen (Aitken &West, 1990), spermatozoa also generate ROS (Holland zyxw et al., 1982; Henkel et al., 1997). Normally, each somatic cell contains protective enzymatic systems against oxidative stress, namely glutathione peroxidase/reductase, catalase and superoxide dismutase (Ryan & Aust, 1992). A possible reason for the extraordinary suscepti- bility of spermatozoa to oxidative stress is the very high content of poly-unsaturated fatty acids in the plasma membrane, especially docosahexanoic acid (Darin-Bennett et al., 1976). This, in comparison with somatic cells, unique composition of phospho- lipids in the sperm plasma membrane is thought to be important for membrane stability, fluidity and permeability (Parks & Hammerstedt, 1985). These special physical-chemical properties of the sperm membrane are responsible for normal sperm function, in which ROS are also supposed to play a physiological role during capacitation (de Lamirande & Gagnon, 1995) by modulating the characteristics of the plasma membrane which is very sensitive to oxidation (Aitken, 1995). In addition, Aitken et al. (1995) showed that ROS might also have a key position in the control of