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Polystyrene microplastics exposure induces growth toxicity and disturbs skeletal muscle angiogenesis via THBS1

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Piglets fed diets containing polystyrene microplastics at 75 and 150 mg/kg for 30 days showed growth toxicity and impaired skeletal muscle angiogenesis. The study found that microplastic exposure disrupts vascular development in muscle tissue via the THBS1 signaling pathway.

Abstract Background: Microplastics (MPs) exposure can cause oxidative damage, reproductive toxicity, and inflammatory diseases, attracting global attention. Microvasculature is essential for skeletal development. Its aberrant formation could impair skeletal muscle regeneration. However, the toxic effect of MPs exposure on skeletal muscle angiogenesis remains unclear. Results: In vivo, piglets were given diets containing 0 mg/kg (CON group), 75 mg/kg (75 mg/kg MPs group), and 150 mg/kg polystyrene MPs (150 mg/kg MPs group) with particle sizes of 1.23 μm for 30 days. The findings revealed that the average daily gain of piglets in the 150 mg/kg MPs group was lower than that in the CON group. Increased MPs accumulation in skeletal muscle in the 150 mg/kg MPs group resulted in a lower redness index, myoglobin content, and type I muscle fiber, along with a rise in type II muscle fiber. Metabolomic analysis indicated significant reductions in the levels of carnosine, beta-Alanine, palmitic acid, niacinamide, and glutathione in the skeletal muscle of the 150 mg/kg MPs group compared to the CON group. In addition, piglets treated with 150 mg/kg MPs exhibited heightened oxidative stress and impaired angiogenesis in skeletal muscle. In vitro, MPs treatment hindered the proliferation, migration, and tube formation of porcine vascular endothelial cells in vitro . Further mechanistic investigation revealed that MPs up-regulated the expression of thrombospondin 1 (THBS1) by reducing mRNA and protein degradation, thus disrupting skeletal muscle angiogenesis. Conclusions: MPs exposure limits the growth of piglets and increases the oxidative damage in skeletal muscle. In addition, MPs exposure induces type II muscle fiber formation and diminishes skeletal muscle angiogenesis through THBS1. These results contribute to a better understanding of MPs toxicology in growth and skeletal muscle development of both animals and humans.

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