The presence of microplastics in human semen and the protective role of nicotinamide mononucleotide against polystyrene nanoplastics-induced reproductive and early embryonic toxicity.

Nano(micro)plastics (NMPs) are ubiquitous environmental pollutants that pose significant potential risks to male reproductive health. However, their size-dependent effects on human sperm and the underlying mechanisms remain poorly characterized, and effective interventions are lacking. This study utilized both human and mouse models to evaluate the reproductive hazards of polystyrene nanoplastics (PS-NPs), while also investigating the protective role of nicotinamide mononucleotide (NMN) as a potential intervention. Using laser direct infrared spectroscopy (LDIR), we detected microplastics (MPs) in human semen samples, with polystyrene among the most prevalent polymers. In vitro, 500 nm PS-NPs dose-dependently impaired sperm motility, increased reactive oxygen species (ROS), and disrupted mitochondrial membrane potential (MMP) and DNA fragmentation index (DFI), all of which were effectively reversed by NMN via the restoration of cellular antioxidant capacity. In vivo, paternal PS-NPs exposure induced transcriptomic disturbances in testes-including enrichment of inflammation and extracellular matrix dysfunction pathways-and compromised sperm quality and early embryonic development, accompanied by elevated embryonic ROS. Crucially, NMN co-treatment ameliorated these alterations and substantially normalized transcriptional profiles, particularly rescuing pathways related to reproduction and embryo development. This study provides observational evidence of the presence of MPs in human semen using LDIR. Our findings demonstrate that 500 nm PS-NPs cause functional sperm damage through mitochondrial oxidative stress, while establishing NMN as a promising therapeutic strategy to mitigate both reproductive and early embryonic toxicity induced by PS-NPs.