HUMAN REPRODUCTION

Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study
Saleh R, Agarwal A, Sharma R, Nelson D, Thomas A
Center for Advanced Research in Human Reproduction, Infertility, and Sexual Function, Urological Institute, Cleveland, Ohio, USA
Fertil Steril. 2002; 78: 491-9

• Objective: To investigate levels of seminal oxidative stress (OS) and sperm quality in a group of infertile men with a history of cigarette smoking.
• Design: A prospective clinical study.
• Setting: Male infertility clinic, Urological Institute, the Cleveland Clinic Foundation, Cleveland, Ohio.
• Patient(s): Infertile men who smoked cigarettes (n=20), infertile men who were nonsmokers (n=32), and healthy nonsmoking donors (n=13).
• Intervention(s): Genital examination, standard semen analysis, sperm DNA damage.
  Main Outcome Measure(S): Levels of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) measured by a chemiluminescence assay and seminal OS assessed by calculating a ROS-TAC score. Sperm DNA damage was measured by sperm chromatin structure assay.
• Result(s): Smoking was associated with a 48% increase in seminal leukocyte concentrations (P<.0001), a 107% increase in ROS levels (P=.001), and a 10-point decrease in ROS-TAC scores (P=.003). Differences in standard sperm variables and DNA damage indices between the infertile smokers and infertile nonsmokers were not statistically significant.
• Conclusion(s): Infertile men who smoke cigarettes have higher levels of seminal OS than infertile nonsmokers. Given the potential adverse effects of seminal OS on fertility, physicians should advise infertile men who smoke cigarettes to quit.
  
  
• Editorial Comment
  Spermatozoa produce low levels of reactive oxygen species (ROS) as part of their aerobic metabolism. Under normal conditions, sperm ROS are physiologically important. However, nonmotile, abnormal spermatozoa, as well as normal ones that are functionally defective, and seminal plasma leukocytes, produce high amounts of ROS. Elevated seminal reactive oxygen species surpasses the seminal plasma total antioxidant capacity. Consequently, lipid peroxidation of sperm membrane polyunsaturated fatty acids may occur. Lipid peroxidation causes intense proteic damage, cytosqueletal modifications, and inhibition of many cellular mechanisms, thus decreasing the individual fertility status. Oxidative stress may damage sperm DNA, and such damage cannot be measured by any test of the conventional semen analysis.
  This study advocates that smoking cigarettes places an additional risk to the already compromised fertility in infertile men. Seminal ROS levels in infertile smokers were very high, which can also be explained by an inflammatory reaction, as evidenced by an increase in the number of seminal leukocytes. It has been shown that leukocytes produce much higher amounts of ROS than spermatozoa. On the other hand, this study did not show any differences in conventional sperm parameters between infertile men who smoke or not. These results are expected, and reiterates what was said about oxidative stress and conventional sperm parameters in the last paragraph. Surprisingly, the authors could not show increased sperm DNA damage in infertile smokers, despite the elevated ROS levels in these individuals. The inclusion of an additional group of healthy smokers could strengthen the study by reiterating the negative impact of smoking cigarettes on the fertility potential of otherwise fertile men.
  Besides the preventive approach as proposed by the authors, strategies to minimize oxidative stress have been studied. However, oral supplementation with antioxidants such as vitamin C and E, among others, is merely empirical to date (1).

Reference
1. Rolf C, Cooper TG, Yeung CH, Nieschlag E: Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod. 1999; 14:1028-33.

Dr. Sandro C. Esteves
Androfert
Campinas, SP, Brazil