This review reports current knowledge regarding the roles that cadmium (Cd), mercury (Hg), arsenic (As), lead (PB), manganese (Mn), and zinc (Zn) play as endocrine-disrupting chemicals (EDCs). The influence of these metals on the endocrine system, possible mechanisms of action, and consequent health effects were correlated between experimental animals and humans. Analysis of the studies prompted us to identify some critical issues related to this area and showed the need for more rigorous and innovative studies. Consequently, it was recommended that future studies need to: (1) identify the mechanisms of action, because at the present time only a few have been elucidated-in this context, the possible presence of hormesis need to be determined, as currently this was reported only for exposure Cd and As; (2) study the possible additive, synergistic, or antagonistic effects on the endocrine system following exposure to a mixture of metals since there is a lack of these studies available, and in general or occupational environments, humans are simultaneously exposed to different classes of xenobiotics, including metals, but also to organic compounds that might also be EDCs; (3) assess the potential adverse effects on the endocrine system of low-level exposures to metals, as most of the information currently available on EDCs originates from studies in which exposure levels were particularly high; and (4) assess the effects on the endocrine and reproductive systems of other metals that are present in the general and occupational environment that have not yet been evaluated.

The Effects of Metals as Endocrine Disruptors

Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial.

DNA fragmentation is an important factor in the aetiology of male infertility. However, it is still underevaluated and its inclusion in routine semen analysis is debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. Couples may be counselled to proceed directly to intracytoplasmic sperm injection as it is more successful in this group, avoiding costly procedures, recurrent failures or pregnancy losses; however, this treatment is not without limitations or risks. Ideally DNA fragmentation should be minimized where possible. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed, and in many cases are shown to be easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential functions, including fertilization. Reducing oxidative stress may improve a couple's chances of conception either naturally or via assisted reproduction. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible. DNA fragmentation is an important factor in the aetiology of male infertility. However it is still underevaluated and its inclusion in routine semen analysis is still debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high levels of DNA fragmentation will have significantly lower odds of conceiving naturally or through procedures such as intrauterine insemination and IVF. Intracytoplasmic sperm injection (ICSI) may be much more successful in this group, and couples may be counselled to proceed directly to ICSI, avoiding costly procedures, recurrent failures or pregnancy losses. However, ICSI is not without its limitations or risks. Ideally, DNA fragmentation should be investigated and minimized where possible in men trying to conceive naturally or through assisted reproduction technology. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed and in many cases are easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential sperm function, including fertilization. Reducing oxidative stress may improve a couple's chances of conception either naturally or via assisted reproduction treatment. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible.

https://www.rbmojournal.com/article/S1472-6483(14)00118-7/pdf

Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility.

BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and b-carotene) is associated with semen quality. METHODS: Ninetyseven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P 5 0.04), concentration (P 5 0.05) and TPMS (P 5 0.09); between vitamin E intake and progressive motility (P 5 0.04) and TPMS (P 5 0.05); and between b-carotene intake and sperm concentration (P 5 0.06) and progressive motility (P 5 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.

Antioxidant intake is associated with semen quality in healthy men

Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men

The aim of the study was to examine the relationships between concentrations of zinc in blood and seminal plasma and sperm quality among infertile and fertile men. One hundred seven male (infertile group) partners of couples who were undergoing investigation for infertility with no known cause for the infertility and 103 men (fertile group) whose wives were pregnant at the time of the study were recruited. The subjects' blood and seminal plasma concentration of zinc were determined by atomic absorption spectroscopy. Except for semen volume, all the other semen parameters for the infertile men were significantly lower than those for the fertile group. The geometric means of the seminal plasma zinc concentration were significantly lower in the infertile group compared with those in the fertile group; 183.6 mg/L (range, 63-499) versus 274.6 mg/L (range, 55-420). There were no significant differences in the geometric means of the blood zinc concentration between the 2 groups. Seminal plasma zinc concentration was significantly correlated with sperm density (r = 0.341, P < .0001), motility (r = 0.253, P < .0001), and viability (r = 0.286, P < .0001). On the basis of the findings of this study and those of other reports, zinc may contribute to fertility through its positive effect on spermatogenesis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.1939-4640.2000.tb03275.x

Comparison of zinc concentrations in blood and seminal plasma and the various sperm parameters between fertile and infertile men.

The aim of the study was to determine whether there were significant 'seasonal' variations in the rhythm of sperm parameters (i.e. semen volume and sperm density) of men who reside in the tropics. A total of 7656 semen analysis results from the department of obstetrics and gynaecology of a tertiary general hospital was analysed. These samples were obtained as part of an initial screening for male partners of couples with problems trying to conceive who were attending a fertility clinic from 1991 to 1995. The subjects' mean semen volume and sperm density of 2.9 ml and 26.9x10(6)/ml respectively were within the World Health Organization reference values. There were no significant month-to-month variations in the adjusted (for age of subject, year of test and technologist who performed the analysis by analysis of co-variance, ANCOVA) mean semen volume and sperm density over the 5 year period. Variations in semen volume and density observed in the temperate climates are not seen in this study, which was conducted in subjects staying in the tropics. This observation may be related to relative constant temperature and hours of light exposure among men who reside in the tropics. As this study is, so far, published data from only one country, Singapore, it may not truly reflect the actual situation for individuals who are residing in the tropics.

Lee-Mee Ho

Papers

Comparison of zinc concentrations in blood and seminal plasma and the various sperm parameters between fertile and infertile men.

Monthly variation in human semen quality in male partners of infertile women in the tropics

The impact of smoking on seminal biomarkers in subfertile men