Unveiling the Insidious Role of Polystyrene Nanoplastics in Compromising Male Fertility.

Global male reproductive health has undergone a marked decline, paralleling the increasing environmental burden of polystyrene nanoplastics (PS-NPs). This review integrates human, rodent, and in vitro evidence on PS-NP-induced male reproductive toxicity, emphasizing on testis and prostate pathology, epigenetic inheritance, gut-testis axis disruption, and co-exposure with environmental mixtures. PS-containing particles or unresolved micro/nanoplastics have been found in human semen and testicular tissue. Rodent studies show PS-NPs can cross epithelial barriers, and spread to the testes. PS-NPs induce oxidative stress; perturb mitochondrial homeostasis and endoplasmic reticulum stress; dysregulate endocrine signaling; and drive epigenetic reprogramming, together with gut-testis axis dysbiosis and metabolic remodeling collectively undermine germ cell development and sperm maturation. Co-exposure to heavy metals, plasticizers, or persistent organic pollutants exacerbates PS-NP toxicity, highlighting the realistic relevance of mixture effects. Furthermore, this review evaluates promising countermeasures, including natural compounds and engineered nanomaterials that mitigate oxidative damage, restore redox balance, and preserve testicular integrity. By integrating human exposure evidence, experimental pathophysiology, multi-pollutant interaction models, and intervention strategies, this review reconceptualizes PS-NP-driven reproductive injury not as a localized testicular injury, but as a systemic, environmentally mediated disorder with diverse biological impacts. This highlights the urgent need for strengthened surveillance, evidence-based regulatory policies, and targeted public health interventions to address nanoplastic pollution.