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Microplastics (MPs) are considered as a pollutant of marine environments and have become a global environmental problem in recent years. A number of studies have demonstrated that MPs can enter the human food chain, and MPs have even been detected in human stools. Therefore, there is increasing concern about the potential risks of MPs to human and animal health. Here, we investigated maternal polystyrene MPs exposure during gestation and lactation and evaluated the potential effects on dams and the F1 (both PND 42 and 280) and F2 (PND 42) generations. The results of transcriptome and 16S rRNA sequencing indicated that MPs caused the metabolic disorder in maternal MPs associated with gut microbiota dysbiosis and gut barrier dysfunction. Simultaneously, maternal MPs exposure also had the intergenerational effects and even caused long-term metabolic consequences in the F1 and F2 generations. In addition, in F1 (PND 42), the composition of gut microbiota did not change significantly, while the hepatic transcriptome and serum metabolite changes showed the potential risk in metabolic disorder. Then, the potential of hepatic lipid accumulation was observed in adult F1 mice (PND 280), especially in the female mice. Our results demonstrated that maternal MPs exposure during gestation and lactation increases the risk of metabolic disorder, and these results provide new insight into the potential long-term hazards of MPs.

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