EDCs: Focus on reproductive alterations in males

Many andrological pathologies seen in adults, including infertility, actually arose in younger age, due to the strong susceptibility and vulnerability of male gonads to external insults, starting from gestation age and during all growth phases. Three main phases are particularly susceptible to subsequent normal testis development and function: the intrauterine phase and the neonatal phase comprising the so-called minipuberty and puberty. However, even during infancy, damaging causes permanent effects on testicular function. Among risk factors for alterations of sexual and reproductive organs and function, endocrine-disrupting chemicals (EDCs) have gained particular attention in the past decades, given their ability to disrupt them at different levels and at different ages, with long-term consequences and possibly also transgenerational effects. Bisphenol, phthalates, perfluoroalkyl substances, heavy metals, and dioxins are particularly intriguing, given the strong experimental evidence of effects on hormone nuclear receptors, hypothalamus-pituitary-testis axis, and direct action on spermatogenesis and steroidogenesis. Although epidemiological studies in humans have shown controversial and inconsistent results, the overall conclusion points toward a positive association between exposure to EDCs and alteration of the reproductive system.