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

Nano Letters 2025 9 citations ? Citation count from OpenAlex, updated daily. May differ slightly from the publisher's own count.
Ruiqiong Li, Xifeng Wang, Jinjin Zhang, Yinchu Hu, Yuxin Yang, Ying Zhang, Boqing Li, Meidi Shen, Chongkun Wang, Yuanyuan Yang, Xiaodong Song, Lihua Ren, Lianshuang Zhang

Summary

When pregnant mice were exposed to polystyrene nanoplastics, the particles crossed into offspring hearts and caused heart damage through a process called ferroptosis, a type of iron-dependent cell death. The nanoplastics activated a specific molecular pathway involving HIF-1 alpha and HO-1 that led to iron buildup, mitochondrial injury, and oxidative stress in heart tissue. This study raises concerns that maternal nanoplastic exposure during pregnancy could harm fetal heart development in ways that may have lasting consequences.

Polymers
Body Systems
Models

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.

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