Infertile Men Who Smoke Carry A High Risk Of Seminal Oxidative Stress
Ashok Agarwal, Ph.D. and Anthony J.Thomas Jr., M.D.
Although cigarette smoking is a widely recognized health hazard and a major cause of mortality, humans continue to consume cigarettes on a regular basis. Approximately one-third of the world's population who are 15 years of age and older smoke cigarettes daily. Given the large number of men worldwide who smoke and the fact that cigarette smoke is a known somatic cell mutagen and carcinogen, there has been a major concern that smoking may adversely affect male reproductive health. The impact of cigarette smoking on male fertility remains a highly controversial issue.
A number of studies have shown that smoking has a detrimental effect on sperm quality, most significantly sperm concentration, motility, and morphology. In addition, cigarette smoking has been correlated with poor sperm function in sperm penetration assays and paternal smoking has been associated with a significant increase in the percentage of spermatozoa with DNA damage which could lead to higher risk of birth defects and childhood cancers in the offspring.
There are also a few studies that have not found an association between smoking and sperm quality, sperm functions, or sperm nuclear DNA damage. Such contradictory data could, in part, be due to the fact that the studies were conducted on 2 different populations: normal, healthy men and infertile men. Some studies did not take into consideration confounding factors such as exposure to other toxins and genital examination abnormalities.
A recent prospective study from our center investigated the semen quality, levels of seminal oxidative stress (OS), and sperm DNA damage in a group of infertile men who smoked cigarettes on regular basis. Information on smoking habits was obtained from 52 infertile men at the time of clinical examination. Standard semen analysis was performed according to World Health Organization guidelines (WHO, 1999). Seminal leukocyte concentrations were determined by a myeloperoxidase-staining test. Levels of reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured by a chemiluminescence assay. A composite value of ROS-TAC score was calculated as an index for OS (seminal OS increases as the ROS-TAC score decreases). Sperm nuclear DNA damage was assessed by sperm chromatin structure assay (SCSA). Results were expressed as %COMPat, which represents the percentage of cells outside the main population of sperm that have abnormal chromatin structure.
Based on the history and results of a genital examination, the patients were classified into 1 of 4 groups: group 1, smokers with a normal genital examination (n = 12); group 2, nonsmokers with a normal genital examination (n = 21); group 3, smokers with an abnormal genital examination (i.e. varicocele, n = 8); and group 4, nonsmokers with an abnormal genital examination (i.e. varicocele, n = 11). A group of healthy nonsmoker sperm donors (n = 13) was included as a control for the study. All donors had a normal genital examination.
Standard sperm parameters (sperm concentration, motility, and morphology) were not significantly different in the infertile men who smoked than that of the non-smokers (Table 1). Comparisons of ROS, TAC and ROS-TAC score between the donors and the 4 study groups are shown in Tables 2 and 3. After adjusting for the abnormal genital examination (varicocele) and the infertility status, smoking in infertile men was associated with 48% increase in seminal leukocyte concentration (P < 0.0001), 107% increase in seminal ROS levels (P = 0.0003), and an 11 point decrease in ROS-TAC scores (P = 0.002). The %COMPat was significantly higher in group 1 [26 (17, 28)] and group 3 [38 (27, 41)] than that of the normal donors [14 (10, 22)] (P = 0.02 & P = 0.0001, respectively). However, the difference in %COMPat between the infertile smokers and nonsmokers was not statistically significant (P > 0.28).
In conclusion, our study found a strong relationship between cigarette smoking and increased levels of seminal OS in infertile men. Such a relationship may be, at least in part, due to the significant increase in seminal leukocyte concentrations observed in infertile smokers. Smoking metabolites may cause sub-clinical inflammation in the male reproductive tract and recruitment of leukocytes, which in turn results in oxidative burst and OS. Detrimental effects of smoking on standard sperm parameters (concentration, motility and morphology) and levels of sperm DNA damage may be masked because of the infertility status. Given the potential adverse effects of OS on fertility, physicians should advise infertile men who smoke cigarettes to quit.
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