Impact of Endocrine Disruptors on Male Sexual Development

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 gestational age and during all growth phases. Three main phases are particularly susceptible for normal testis development and function: the intrauterine phase, the neonatal phase comprising the so-called minipuberty, and puberty. However, even during infancy, when the testes are apparently “sleeping,” damaging causes with permanent effects on testicular function can occur. Among risk factors for alterations of sexual and reproductive organs and function, endocrine-disrupting chemicals (EDCs) have gained particular attention in the last decades, given their ability to disrupt them at different levels and at different ages, with long-term consequences and possibly also transgenerational effects. Bisphenol A, phthalates, and perfluoroalkyl substances are particularly intriguing chemicals, given the strong experimental evidence suggesting 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 male reproductive system.