Prenatal and postnatal exposure to environmental level arsenic declines male reproductive function by affecting spermatogenesis and maturation in offspring.

Arsenic contamination in water, soil, and food is of global health concern, however, the relationship between real-life arsenic exposure and male reproductive toxicity risk of the emerging adult population is unclear, and the effective early warning targets are lacking. To address this, a model of mouse exposed to environmental levels of arsenic (0, 0.02, 0.1 and 0.5 mg/L As2O3) via drinking water from 4 weeks prior to mating maternally until offspring maturity (PND161) was established, 50 parameters related to male reproduction were systematically assessed. The results showed that arsenic exposure led to a decrease in sperm motility and sperm count, and an increase in sperm malformation rate from PND91 to PND161 of offspring. Arsenic also impaired spermatogenesis and sperm maturation by differentially affecting testicular meiosis and epididymal key proteins. Notably, most changes in the evaluated parameters exhibited a dose-response relationship with the increase of the arsenic exposure period. Besides, sperm motility, sperm malformation rate, Ovch2 expressions in epididymis, and testicular Bcl2, Sycp3, Stag3 expression were the most closely associated with changes in hair arsenic levels. This study provides a basis for the assessment of the risk of real-life arsenic exposure on children's reproductive health, alongside the identification of sensitive biomarkers for monitoring, diagnosis, and environmental assessment.