Arsenic Toxicity in Male Reproduction and Development

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.