Co-exposure to polystyrene nanoplastics and hexachlorocyclohexane induces enhanced human sperm toxicity in vitro

The decline in global male fertility has been increasingly linked to exposure to environmental contaminants. This study investigates the combined toxicity of polystyrene nanoplastics (PS-NPs) and hexachlorocyclohexane (HCH, a type of persistent organic pollutants (POPs)) on human sperm function in vitro. Sperm samples from healthy donors were exposed to PS-NPs, HCH, or both, and key functional parameters, including motility, penetration ability, capacitation, acrosome reaction, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) were assessed. Results demonstrated that co-exposure to PS-NPs and HCH could enhance toxicity to cause a marked decline in sperm viability, motility, and penetration capacity compared to individual exposures. Moreover, co-treatment markedly elevated intracellular ROS ([ROS]_i), reduced MMP, and inhibited progesterone-induced capacitation and acrosome reaction. Network pharmacology and the followed western blot (WB) analysis demonstrated an upregulation of pro-apoptotic proteins (Caspase-3 and Bax) and downregulation of Bcl-2, indicating activation of mitochondrial apoptotic pathways. These findings provide the first evidence that co-exposure to PS-NPs and HCH could induce enhanced spermatotoxicity, likely attributable to oxidative stress and mitochondrial dysfunction, highlighting a potential environmental risk factor in idiopathic male infertility.