Microplastic particles (MP) are prevalent in both industrial production and the natural environment, posing a significant concern for human health. Daily diet, air inhalation, and skin contact are major routines of MP intake in human. The main injury target systems of MPs include the digestive system, respiratory system, and cardiovascular system. However, the study on MPs' adverse effects on the heart is less than other target organs. Previous in vivo studies have demonstrated that MPs can induce heart injuries, including abnormal heart rate, apoptosis of cardiomyocytes, mitochondrial membrane potential change, and fibrin overexpression. To address animal welfare concerns and overcome inter-species variations, this study employed a human pluripotent stem cell-derived in vitro three-dimensional cardiac organoid (CO) model to investigate the adverse effects of MPs on the human heart. The distinct cavities of COs allowed for the observation of MPs' aggregation and spatial distribution following polystyrene-MP (PS) exposure in a dynamic exposure system. After exposure to various concentrations of PS (0.025, 0.25 and 2.5 µg/mL, with the lowest concentration equivalent to human internal exposure levels), the COs exhibited increased oxidative stress, inflammatory response, apoptosis, and collagen accumulation. These findings were consistent with in vivo observations, in terms of increases in the interventricular septal thickness. The expression of hypertrophic-related genes of COs (MYH7B/ANP/BNP/COL1A1) changed noticeably and the cardiac-specific markers MYL2/MYL4/CX43 were also markedly elevated. Our findings revealed the PS could induced cardiac hypertrophy in vivo and in vitro, indicating that MP may be an under-recognized risk factor for cardiovascular system.

Fine particulate matter (PM_2.5) has been implicated as a risk factor for neurodevelopmental disorders including autism in children. However, the underlying biological mechanism remains unclear. DNA methylation is suggested to be a fundamental mechanism for the neuronal responses to environmental cues. We prepared whole particle of PM_2.5 (PM_2.5), water-soluble extracts (Pw), organic extracts (Po) and carbon core component (Pc) and characterized their chemical constitutes. We found that PM_2.5 induced significant redox imbalance, decreased the levels of intercellular methyl donor S-adenosylmethionine and caused global DNA hypomethylation. Furthermore, PM_2.5 exposure triggered gene-specific promoter DNA hypo- or hypermethylation and abnormal mRNA expression of autism candidate genes. PM_2.5-induced DNA hypermethylation in promoter regions of synapse related genes were associated with the decreases in their mRNA and protein expression. The inhibiting effects of antioxidative reagents, a methylation-supporting agent and a DNA methyltransferase inhibitor demonstrated the involvement of redox/methylation mechanism in PM_2.5-induced abnormal DNA methylation patterns and synaptic protein expression. The biological effects above generally followed a sequence of PM_2.5 ≥ Pwo > Po > Pw > Pc. Our results implicated a novel epigenetic mechanism for the neurodevelopmental toxicity of particulate air pollution, and that eliminating the chemical components could mitigate the neurotoxicity of PM_2.5.