**1.5.7 Tobacco smoke**

It is beyond the scope of this review to provide a detailed review of the literature on cigarette smoking and semen quality. However, PAH (polycyclic aromatic hydrocarbons), the major carcinogenic components of cigarette smoke (Vine, 1996), were found to activate aryl hydrocarbon receptor (AhR), suggesting that tobacco smoke may represent a chemical mixture with endocrine disrupting activity. There is extensive evidence demonstrating that exposure to tobacco smoke is associated with reduced semen quality (Vine, 1996). An inverse dose-dependent relationship between smoking and semen volume, total sperm count, and percent motile sperm was reported following a large cross-sectional study of 2542 healthy Danish men. Sperm concentration was 19% lower in heavy smokers compared to non-smokers. Serum LH and testosterone were positively correlated with smoking (Ramlau-Hansen et al., 2007). The incidence of bilateral cryptorchidism in a sample of cryptorchid Danish boys was increased in children of smoking mothers. Testicular biopsies from boys exposed in utero/neonatal to tobacco smoke demonstrated a decreased number of spermatogonia and gonocytes per tubule cross section (Thorup et al., 2006). Similarly, a large cross-sectional European study of 889 Danish men, 221 men from Norway, 313 Lithuanian men, and 190 men from Estonia reported reductions of sperm concentrations by 20% in sons exposed to prenatal tobacco smoke (Jensen et al., 2004), while a separate study described an inverse dose-dependent association between sperm concentration and prenatal tobacco exposure, measured in adult sons of 522 Danish women (Jensen et al., 2005). The association between impaired semen quality and smoking is fairly well established (Vine, 1996). Although epidemiological studies of male reproductive function were designed to avoid the confounding effects of smoking, by limiting samples to non-smokers or segmenting samples according to smoking status, the interaction effects of tobacco smoke, alcohol, and other lifestyle factors are often not considered. An important study by Robbins et al.,(1997) did investigate the interactions of caffeine, alcohol, and cigarette smoking on sperm aneuploidy, determining that incidence of sperm abnormalities decreased after controlling for age and other lifestyle factors.
