Relationships between Toenail, Urinary, and Drinking-water Fluoride Concentrations in a Pregnancy Cohort using Private Water Systems in the United States.

Infertility has become a serious global health concern, affecting 8–12% of reproductive age couples. Among many factors, male factor contributes to 20–30% of the overall infertility [], but the causes of male subfertility can be numerous which remain poorly understood []. Among potential risk factors, environmental and occupational exposure to toxic chemicals has recently received increasing attention []. Mercury (Hg), a naturally occurring element that can be transported globally via long-range atmospheric transport and landed via dry and wet deposition []. Once landed, inorganic Hg [; e.g., Hg(II)] can be converted by a suite of anaerobic microbes in reducing environments (e.g., surface sediments) into highly toxic methylmercury () []. In fact, MeHg can extensively bioaccumulate at the base of aquatic food webs and increase its concentrations along the food chain, leading to very high levels in the top predators in the aquatic environment []. In the general population, MeHg exposure is largely driven by fish and seafood consumption, whereas elemental Hg () exposure is commonly associated with dental amalgams [, ]. Occupational Hg exposure, in contrast, is mainly relevant to specific populations, such as artisanal gold miners and dental professionals [, ]. Experimental studies using mammalian animal models have consistently shown that exposure to Hg compounds across a range of routes and doses can impair male reproductive functions, including disrupted spermatogenesis, reduced sperm motility and histopathological damage to the seminiferous epithelium [, , , , ]. Within the testis, the blood-testis barrier (BTB), formed by desmosomes, gap junctions, tight junctions, and basal ectoplasmic specialization, create a protective essential microenvironment for spermatogenesis [, , ]. Animal studies have previously identified that exposure to Hg disrupts the BTB by inducing oxidative stress, cytoskeletal disorganization, and junctional protein loss, leading to increased barrier permeability, impaired sperm quality, and reduced fertility [, –, ]. However, translating these findings to human populations remains limited and challenging [].