Endocrine-disrupting chemicals in male reproductive health: exposure risks, reproductive toxicity and emerging perspectives.

Abstract

Male reproductive health represents a growing global health challenge, and increasing evidence highlights the contribution of environmental exposures to declining male reproductive function. Endocrine-disrupting chemicals are widespread environmental contaminants that interfere with endocrine regulation and have been associated with impaired semen quality, hormonal imbalance and testicular dysfunction. Here, we summarize current advances in understanding EDC-induced male reproductive toxicity, focusing on major chemical classes, including bisphenols, phthalates, pesticides, per- and polyfluoroalkyl substances and heavy metals. We discuss the interconnected mechanisms underlying reproductive impairment, including disruption of the hypothalamic-pituitary-gonadal axis, altered steroidogenesis, oxidative stress, mitochondrial dysfunction, blood-testis barrier disruption, immune dysregulation and epigenetic reprogramming. Importantly, emerging evidence from developmental origins of health and disease perspectives indicates that exposure during critical developmental windows may establish persistent molecular alterations, influencing reproductive outcomes across the life course. In addition, the metabolic effects of certain EDCs, including obesity and metabolic dysfunction, may further exacerbate male reproductive impairment. Given that human exposure occurs predominantly in the form of complex chemical mixtures, future research should integrate exposomics, multi-omics approaches and longitudinal cohorts to clarify causal relationships and identify susceptible populations. Such advances will be essential for developing precision environmental health strategies to preserve male reproductive function.