BackgroundNanoplastics can be considered a novel contaminant for the environment because of their extensive applications in modern society, which represents a possible threat to humans. Nevertheless, the negative effect of polystyrene nanoplastics (PS‐NPs) on male reproduction, fertility, and progeny outcomes is not well known. Thus, the aim of the present work was to calculate the median lethal dose (LD50) and investigate the consequences of exposure to PS‐NPs (25 nm) on male reproductive toxicity.MethodsThis investigation first determined the LD50 of PS‐NPs in male Wistar rats, and then in a formal study, 24 rats were distributed into three groups (n = 8): the control group; the low‐dose group (3 mg/kg bw); and the high‐dose group (10 mg/kg bw) of PS‐NPs administered orally for 60 days. On the 50th day of administration, the fertility test was conducted.ResultsThe LD50 was determined to be 2500 mg/kg. PS‐NP administration induced significant alternations, mainly indicating mortality in the high‐dose group, a significant elevation in body weight gain, declined sperm quality parameters, altered reproductive hormonal levels, thyroid endocrine disruption, an alternation of the normal histo‐architecture and the histo‐morphometric analysis of the testes, and impaired male fertility.ConclusionAltogether, the current findings provide novel perspectives on PS‐NP general toxicity with specific reference to male reproductive toxicity.