MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007- )
Principal Investigator: Spomenka Telišman (until 31 December 2007), Alica Pizent (since 1 January 2008)
Recent evidence has indicated a deterioration in the reproductive health of men in many countries over the past few decades, particularly a decrease in semen quality and an increase in prevalence of prostate cancer, but also great differences between and within some countries. The cause of these phenomena is unknown, although a complex role of environmental and lifestyle factors has been implicated. Lead (Pb) and cadmium (Cd) are toxic metals, pervasive in the human environment and accumulate in the human body over a lifetime. In addition to direct toxicity, they can interfere with the metabolism of several essential metals by reducing their bioavailability in the body, can contribute to oxidative stress (implicated in the pathogenesis of male infertility), and can inhibit DNA repair. Copper (Cu), zinc (Zn) and selenium (Se) are essential elements required for optimum activity of many enzymes, including the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) that are protective against oxidative stress. Particularly Zn and Se are important for male reproductive function and can reduce the toxicity of Pb and Cd. Varicocele belongs to the most important causes of male infertility, although the mechanism behind its adverse action is poorly known. Recent data indicate the association of varicocele with an increase in Cd and a decrease in Zn, and with altered activity of antioxidant enzymes in men. Prostate cancer is the 4th most common cancer in men worldwide, and the most common cancer in men in the USA as well as in Croatia. Recent data show a protective role of relatively high serum Se levels against the risk of prostate cancer in men, whereas chronic exposure to Pb and Cd has been shown to decrease Zn and Se, and cause impaired secretory function or damage of the prostate. The objective of this study is to determine the inter-relationship of the blood levels of Pb and Cd, serum levels of Cu, Zn and Se, activities of SOD and GPx in blood, and age, smoking, and alcohol consumption with respect to clinically defined presence and intensity of varicocele, and of prostate damage, in men with no occupational exposure to metals. The purpose is to provide relevant data concerning the etiology, possible substitutional therapy, and prevention of a further deterioration in the reproductive health in men, as well as to evaluate the contribution of each specific environmental and lifestyle factors. The study is important in view of a considerably lower serum Se level, and somewhat higher blood Pb and Cd levels, in the general population of Croatia than in many other countries.