Fluoride toxicity in the male reproductive system.

This review covers the current scientific understanding of the links between environmental exposure to fluoride (F) and its known or potential effects on human male fertility. The most important consequences of these F exposures are: changes in the structure and functional behavior of spermatozoa, disruption of spermatogenesis, and disturbances of multiple hormone systems that impact male reproduction. The changes in spermatozoa result from oxidative damage, zinc deficiency, and disturbed signal transduction. There is evidence that F interferes with spermatogenesis by depressing levels of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR), modifying G-protein signaling, diminishing levels of testosterone and its androgen receptor (AR), and disturbing levels of estradiol. Furthermore, F is also known to interfere with thyroid hormone metabolism, which directly and indirectly impacts not only spermatogenesis but also other reproductive functions. Although F appears to exert its toxic effects in the male reproductive system through these pathways, the molecular details are still poorly understood. The growing evidence that F overexposure leads to male reproductive toxicity through multiple pathways indicates that an assessment of chronic F exposures in human and animal populations is urgently required.