HIF-1α/HO-1-Mediated Ferroptosis Participates in Polystyrene Nanoplastics-Induced Intergenerational Cardiotoxicity

To explore the intergenerational cardiotoxicity of nanoplastics, maternal mice were exposed to 60 nm polystyrene nanoplastics (PS-NP) during pregnancy and lactation. The results showed that PS-NP can enter the hearts of offspring and induce myocardial fiber arrangement disorder, acidophilic degeneration of cardiomyocytes, and elevated creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) levels after maternal exposure to PS-NP at 100 mg/kg during pregnancy and lactation. Mechanistically, KEGG analysis of RNA sequencing showed the participation of hypoxia-inducible factor-1 (HIF-1) and ferroptosis in PS-NP-induced cardiotoxicity. Key features of ferroptosis, including Fe²⁺ accumulation, mitochondrial injury, oxidative stress, GPX4 downregulation, and FTH1, ACSL4, and SLC7A11 upregulation, were detected. Furthermore, PS-NP treatment upregulated the expressions of HIF-1α and HO-1, and PS-NP-induced ferroptosis can be alleviated by inhibition of HIF-1α using si-HIF-1α. This study provided an insightful reference for the intergenerational cardiotoxicity assessment of PS-NP.