Maternal exposure to polystyrene nanoplastics during gestation and lactation impaired skeletal growth in progeny mice by inhibiting neutrophil extracellular trap formation

Microplastics and nanoplastics are widely distributed in the natural environment and shown to accumulate in living organisms. While their potential impact on human health has been investigated, significant uncertainties remain regarding their toxic effects and mechanisms of interaction with the human skeletal system. We examined the potential effects of polystyrene nanoplastics (PS-NPs, 100 nm) on skeletal health and the underlying molecular mechanisms using the human RAW264.7 and MC3T3-E1 cell lines as in-vitro models, along with a murine model. Maternal exposure to PS-NPs (10 mg/L) through drinking water during the prenatal and lactational periods led to an increase in osteoblasts, as well as a significant rise in bone mineral density (BMD) and bone content in offspring mice. Exposure to 100 mg/L PS-NPs resulted in a significant reduction in the thickness of the femoral growth plates. Multi-omics analysis revealed that both high (100 mg/L) and low (10 mg/L) maternal PS-NP exposure concentrations disrupted gene expression and metabolic regulation in the skeletal system of offspring mice. Regulatory analysis showed PS-NPs probably induced inflammation and abnormal immune infiltration levels by inhibiting the formation of neutrophil extracellular traps (NETs), especially in 100 mg/L exposure. In in-vitro tests, the PS-NPs dose-relatedly reduced the relative viability of RAW264.7 cells and promoted osteoclast differentiation, but did not affect MC3T3-E1 cells up to 500 mg/L. Our findings demonstrate that maternal exposure to PS-NPs has detrimental effects on skeletal development and function in progeny mice, providing new insights into their toxicological effects on the skeletal system.