Background: Polystyrene nanoplastics (PS-NPs) are becoming increasingly prevalent in the environment with great advancements in plastic products, and their potential health hazard to animals has received much attention. Several studies have reported the toxicity of PS-NPs to various tissues and cells; however, there is a paucity of information about whether PS-NPs exposure can have toxic effects on mammalian oocytes, especially livestock. Herein, porcine oocytes were used as the model to investigate the potential effects of PS-NPs on mammalian oocytes. Results: The findings showed that different concentrations of PS-NPs (0, 25, 50 and 100 μg/mL) entering into porcine oocytes could induce mitochondrial stress, including a significant decrease in mitochondrial membrane potential (MMP), and the destruction of the balance of mitochondrial dynamic and micromorphology. Furthermore, there was a marked increase in reactive oxygen species (ROS), which led to oocyte lipid peroxidation (LPO). PS-NPs exposure induced abnormal intracellular iron overload, and subsequently increased the expression of transferrin receptor (TfRC), solute carrier family 7 member 11 (SLC7a11), and acyl-CoA synthetase long-chain family member 4 (ACSL4), which resulted in ferroptosis in oocytes. PS-NPs also induced oocyte maturation failure, cytoskeletal dysfunction and DNA damage. Cotreatment with 5 μmol/L ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) alleviated the cellular toxicity associated with PS-NPs exposure during porcine oocyte maturation. Conclusions: In conclusion, PS-NPs caused ferroptosis in porcine oocytes by increasing oxidative stress and altering lipid metabolism, leading to the failure of oocyte maturation. Graphical PS-NPs could enter oocytes, caused mitochondrial dysfunction and oxidative stress, induced lipid peroxidation and ferroptosis, which eventually resulted in failure of oocyte maturation.

Polystyrene nanoplastics (PS-NPs) are ubiquitous in the environment, eliciting significant concerns about their possible risks to human health, especially reproductive health. Various reproductive toxicities of PS-NPs have been reported, however, information regarding the effects of PS-NPs exposure during pregnancy on offspring development and the underlying mechanisms remains limited. In this study, pregnant mice were orally administered PS-NPs (approximately 100 nm in diameter) at different concentrations (1, 10, and 100 mg/kg/day) for 17.5 consecutive days, from gestational day (GD) 0.5 to GD 17.5. The relevant samples were collected on GD 18.5 to investigate the intergenerational effects. The results indicated that PS-NPs induced placental injury and metabolic abnormalities, leading to adverse pregnancy outcomes. Specifically, PS-NPs exposure observably reduced the levels of nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD⁺) in the placenta, resulting in decreased ATP production, increased oxidative stress and ferroptosis. Meanwhile, PS-NPs disrupted the maternal gut microbiome, specifically manifested as a reduction in Lactobacillus levels and abundances of norank_f_Muribaculaceae, Turicibacter, Alloprevotella, Parabacteroides and Ruminococcus. Fecal microbial transplant (FMT) experiments demonstrated that the microbiota from PS-NPs-administered pregnant mice could similarly induce intestinal barrier damages and placental injury. Treatment with NAM effectively mitigated disruptions in placental metabolism and reversed the adverse pregnancy outcomes caused by PS-NPs. These findings highlight the novel role of the gut microbiota in PS-NPs-induced placental injury and adverse pregnancy outcomes, and suggest that NAM could serve as a promising preventative strategy against this intergenerational damage caused by PS-NPs.