**Acknowledgements**

*Male Reproductive Health*

membrane integrity, increasing levels of reactive oxygen species (ROS) and LPO and decreasing the antioxidant activity and diminished fertility ability [62]. Regarding human fertility, in a cross-sectional study, participants with high blood Hg level had lower sperm with a normal morphology [63]. Cd is another male reproductive toxicant that exerts effects even at low levels of exposure by several mechanisms [64]. In vitro studies on human spermatozoa obtained through ejaculation allow to evaluate the effect of Cd treatment in semen parameters [65, 66]. Cd decreased sperm motility and sperm viability and induced detrimental effects on spermatozoa metabolism by inhibition of the activity of glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-diphosphatase, glucose-6-phosphate isomerase, amylase, Mg2+− dependent ATPase and lactic and succinic acid dehydrogenases. As reviewed by de Angelis et al. [33], significant negative correlations were found between Cd levels and semen parameters, including total sperm count, concentration, motility and morphology. Results from a meta-analysis indicate that men with low fertility had higher semen Pb and Cd levels and lower semen Zn levels [67]. Sperm motility was

significantly decreased in men occupationally exposed to Mn [47].

results obtained by in vitro and in vivo studies [76, 77].

**3.2 Sperm DNA damage**

Occupational exposure to pesticides increased the risk of morphological abnormalities in sperm in addition with a decline in sperm count and a decreased percentage of viable spermatozoa. For instance, the exposure to pesticides reduced the seminal volume, sperm motility and concentration and increased the seminal pH and the abnormal sperm head morphology [68–70]. A study showed that young Swedish men exposed to phthalates presented a decrease in progressive sperm motility [71]. Additionally, levels of urinary phthalates and insecticides were also associated with lower sperm concentration, lower motility and increased percentage of sperm with abnormal morphology [72–75]. These results confirmed the

Sperm DNA integrity is essential for the correct transmission of genetic information [78]. Damage at sperm DNA level may result in male infertility. Sperm DNA damage is caused by oxidative stress that causes impairment in the sperm membrane [79]. It is well-known that some EDCs may induce oxidative stress and decrease the cellular levels of GSH and protein-sulfhydryl groups. Preclinical studies with male rats showed that exposure to BPA was associated with a significant increase in sperm DNA damage [80]. A statistically significant positive association between urinary concentrations of parabens and BPA and sperm DNA damage was found in male partners of subfertile couples [53, 81]. Contrary results were obtained by Goldstone et al. [8] that found a negative relationship between BPA and DNA fragmentations. Additionally, other EDCs such as heavy metals (e.g., Hg), PCBs and insecticides induce sperm DNA damage [59, 61, 73, 75, 82–84]. Urinary levels of Hg and nickel in infertile men were associated with increasing trends for tail length, and the levels of Mn were associated with increasing trend for tail distributed moment [82]. The adverse effects of phthalates on sperm DNA were assessed by several studies among infertile men [75, 84]. Urinary concentrations of phthalate metabolites were associated with sperm DNA damage. These studies suggest that environmental and occupational exposure to EDCs may be associated with increased sperm DNA damage.

The results yielded in this chapter showed that both environmental and occupational exposures to EDCs affect male reproductive function at multiple levels.

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**4. Conclusions**

Thanks are due to the support of iBiMED (UID/BIM/04501/2013, UID/ BIM/04501/2019 and POCI-01-0145-FEDER-007628), CESAM (UID/ AMB/50017/2019 and POCI-01-0145-FEDER-007638) and FCT/MEC through national funds. We are also thankful to FCT of the Portuguese Ministry of Science and Higher Education by an individual grant to M.C.H. (SFRH/BD/131846/2017).
