Blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin (EP), blood cadmium (BCd), serum zinc (SZn), seminal fluid zinc (SfZn), serum copper (SCu), and parameters of semen quality and of reproductive endocrine function were measured in 149 healthy male industrial workers 20-43 years of age. The group contained 98 subjects with slight to moderate occupational exposure to Pb and 51 reference subjects. All of the subjects lived in Zagreb, Croatia. Significant (p < 0.05) correlations of BPb, ALAD, and/or EP with reproductive parameters indicated a Pb-related decrease in sperm density, in counts of total, motile, and viable sperm, in the percentage and count of progressively motile sperm, in parameters of prostate secretory function (SfZn, acid phosphatase, and citric acid in seminal fluid), and an increase in abnormal sperm head morphology, serum testosterone, and estradiol. These associations were confirmed by results of multiple regression, which also showed significant (p < 0. 05) influence of BCd, SZn, SCu, smoking habits, alcohol consumption, or age on certain reproductive parameters. These effects were mainly of lower rank and intensity as compared to Pb-related reproductive effects, whereas BCd contributed to a decrease in sperm motility and an increase in abnormal sperm morphology and serum testosterone. No significant Pb- or Cd-related influence was found on levels of the lactate dehydrogenase isoenzyme LDH-C(4) and fructose in seminal fluid or on follicle-stimulating hormone, luteinizing hormone, and prolactin in serum. The seminal fluid concentrations of Pb (SfPb) and Cd (SfCd) were measured in 118 of the 149 subjects, and a highly significant (p < 0.0001) correlation was found between BPb and SfPb levels (r = 0.571) and between BCd and SfCd levels (r = 0.490). The overall study results indicate that even moderate exposures to Pb (BPb < 400 microg/L) and Cd (BCd < 10 microg/L) can significantly reduce human semen quality without conclusive evidence of impairment of male reproductive endocrine function.ImagesFigure 1Figure 2Figure 3Figure 4Figure 5

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Blood lead (BPb), actity of 6-aminolevulinic add dehydratase (ALAD), erythrocyte protoporphyrin (EP), blood cadmium (BCd), serum zinc (SZn), seminal fluid zinc (SaZn), serum copper (SCu), and parameters of semen quality and of reproductive endocrine function were measured in 149 healthy male industrial workers 20-43 years of age. The group contained 98 subjects with slight to moderate occupational exposure to Pb and 51 reference subjects. All of the subjects lived in Zagreb, Croatia. Significant (p < 0.05) correlations of BPb, ALAD, and/or EP with reproductive parameters indicated a Pb-related decrease in sperm density, in counts of total, motile, and viable sperm, in the percentage and count ofprogressively motile sperm, in parameters ofprostate secretory function (S£Zn, acid phosphatase, and citric add in seminal fluid), and an increase in abnormal sperm head morphology, serum testosterone, and estradiol. These associations were confirned by results of multiple regression, which also showed significant (p < 0.05) influence of BCd, SZn, SCu, smoking habits, alcohol consumption, or age on certain reproductive parameters. These effects were mainly of lower rank and intensity as compared to Pb-related reproductive effects, whereas BCd contributed to a decrease in sperm motility and an increase in abnormal sperm morphology and serum testosterone. No significant Pbor Cd-related influence was found on levels of the lactate dehydrogenase isoenzyme LDH-C4 and fructose in seminal fluid or on follide-stimulating hormone, luteinizing hormone, and prolactin in serum. The seminal fluid concentrations of Pb (SfPb) and Cd (SfCd) were measured in 118 of the 149 subjects, and a highly significant (p < 0.0001) correlation was found between BPb and SfPb levels (r = 0.571) and between BCd and SfCd levels (r-=0.490). The overall study results indicate that even moderate

In 123 Croatian men with no occupational exposure to metals, the influence of cadmium on reproductive parameters was examined after adjusting for age, smoking, alcohol, and biomarkers of lead, copper, zinc, and selenium. The following variables were measured: blood cadmium (BCd), blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin, serum copper (SCu), serum zinc (SZn), serum selenium (SSe), activity of glutathione peroxidase (GPx) in blood, testis size, semen quality (including sperm concentration, motility, viability, and morphology), indicators in seminal fluid (the lactate dehydrogenase isoenzyme LDH-C4, fructose, zinc, acid phosphatase, and citric acid), and hormones in serum (follicle-stimulating hormone--FSH, luteinizing hormone, prolactin, testosterone, and estradiol). The median and range BCd values were 2.94 (0.49-11.93) microg/L in 61 smokers and 0.59 (0.20-3.71) microg/L in 62 nonsmokers (p < 0.0001). Smoking habits (cigarettes/day) highly significantly correlated with BCd (p < 0.0001). After adjusting for potential confounding variables by multiple regression, BCd was significantly associated with a decrease in testis size (p < 0.03) and an increase in serum estradiol (p < 0.005), FSH (p < 0.03), and testosterone (p < 0.04). Smoking was significantly associated with a decrease in serum prolactin (p < 0.006) and LDH-C4 in seminal fluid (p < 0.03). Several reproductive parameters were significantly associated with BPb and ALAD, biomarkers of lead, and/or with SCu, SZn, SSe, and GPx. The necessity of controlling for various metals, and other potential confounders when assessing the influence of a particular metal on reproductive function in men, is emphasized.

A combination of genetic, environmental and lifestyle factors contributes to adverse effects on the reproductive health in men. Metals are pervasive in food, water, air, tobacco smoke, and alcoholic beverages. Experimental studies suggest that many metals have adverse effects on the male reproductive function. However, information about reproductive effects of human exposure to metals is scarce and/or inconsistent. This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men. Factors capable of affecting these relationships were identifi ed and discussed. A particular attention is given to the studies considering infl uence of concomitant exposure to various metals. These studies have generally confi rmed that even moderate-to low-level exposure to lead affects certain reproductive parameters, and that exposure to cadmium affects the prostate function and serum testosterone levels. Adverse effects of mercury, manganese, chromium and arsenic on semen quality and altered serum hormone are less well documented. There is no clear evidence that boron exposure may impair reproductive health in men. Only a few studies have investigated reproductive effects of concomitant exposure to several metals and controlled for potential confounders. Future studies should consider the contribution of combined exposure to various metals and/or other factors that may infl uence individual susceptibility to reproductive health impairment in men. KEY WORDS: human semen quality, metals, metalloids, metal interactions, sex hormonesPizent A, et al.