Journal Article

Maternal exposure to nanopolystyrene induces neurotoxicity in offspring through P53-mediated ferritinophagy and ferroptosis in the rat hippocampus

Liu, Xuan, Li, Kang, Shi, Yue, Lin, Bencheng, Zhao, Yiming, Liu, Huanliang, Tian, Lei, Yan, Licheng, Chen, Jiang, Zhang, Yaping, Wei, Yizhe, Lai, Wenqing

2024

Overview

There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Advanced Non-viral Delivery Systems in Tissue Engineering / Analysis / Animals / Apoptosis / Autophagy - drug effects / Biotechnology / Chemistry / Chemistry and Materials Science / Complications and side effects / Female / Ferritinophagy / Ferritins - metabolism / Ferroptosis / Ferroptosis - drug effects / Glutathione - metabolism / Health aspects / Hippocampus - drug effects / Hippocampus - metabolism / Maternal Exposure / Molecular Medicine / Nanoparticles - toxicity / Nanotechnology / Neurons - drug effects / Neurons - metabolism / Neurotoxicity / Polystyrene nanoplastics / Polystyrenes - toxicity / Pregnancy / Prenatal drug exposure / Prenatal Exposure Delayed Effects / Rats / Rats, Sprague-Dawley / Reactive Oxygen Species - metabolism / Tumor proteins / Tumor Suppressor Protein p53 - metabolism