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<p>Polystyrene nanoplastics (PS-NPs) exposure can induce placental toxicity, but the molecular mechanism of PS-NP-induced placental toxicity is poorly understood. We selected PS-NPs (80&#xa0;nm) as a model of plastic particles and treated the human trophoblast cell line JEG3 (6.25, 12.5, 25, 50, and 100&#xa0;mg/L) and pregnant mice with PS-NPs (15, 30 and 60&#xa0;mg/kg·bw). These results found that PS-NPs regulated key ferroptosis-associated proteins (GPX4, ACSL4, and FTH1), indicating that PS-NPs induced ferroptosis. Here, we show for the first time that PS-NPs trigger placental ferroptosis by disrupting the p62-Keap1 interaction, thereby blocking Nrf2 degradation. Although m6A modification of the p62-Keap1-Nrf2 axis has been described in other models, its involvement in nanoplastic-induced placental injury remains unexplored. Here, we showed that PS-NPs induce ferroptosis by promoting <i>METTL3</i> expression in JEG cells and placental tissues. Furthermore, knockdown of <i>METTL3</i> inhibited PS-NP-induced ferroptosis by regulating Keap1 m6A, which inhibited the p62-Keap1-Nrf2 pathway in vitro. PS-NP-induced ferroptosis was attenuated by <i>METTL3</i> knockdown via the inhibition of Keap1 m6A, which regulates the p62-Keap1-Nrf2 pathway. Collectively, these findings indicate thatMETTL3-mediated m6A methylation induced by PS-NPs may represent a previously unrecognized molecular basis for placental injury.</p>

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Polystyrene Nanoplastics induced placental toxicology by activating Keap1-mediated ferroptosis via METTL3-dependent m6A methylation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月3日

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  • Chen Yujiao,
  • Yifan Liu,
  • Meng Zhang,
  • Shanshan Li,
  • Yousheng Yan,
  • Chenghong Yin

摘要

Polystyrene nanoplastics (PS-NPs) exposure can induce placental toxicity, but the molecular mechanism of PS-NP-induced placental toxicity is poorly understood. We selected PS-NPs (80 nm) as a model of plastic particles and treated the human trophoblast cell line JEG3 (6.25, 12.5, 25, 50, and 100 mg/L) and pregnant mice with PS-NPs (15, 30 and 60 mg/kg·bw). These results found that PS-NPs regulated key ferroptosis-associated proteins (GPX4, ACSL4, and FTH1), indicating that PS-NPs induced ferroptosis. Here, we show for the first time that PS-NPs trigger placental ferroptosis by disrupting the p62-Keap1 interaction, thereby blocking Nrf2 degradation. Although m6A modification of the p62-Keap1-Nrf2 axis has been described in other models, its involvement in nanoplastic-induced placental injury remains unexplored. Here, we showed that PS-NPs induce ferroptosis by promoting METTL3 expression in JEG cells and placental tissues. Furthermore, knockdown of METTL3 inhibited PS-NP-induced ferroptosis by regulating Keap1 m6A, which inhibited the p62-Keap1-Nrf2 pathway in vitro. PS-NP-induced ferroptosis was attenuated by METTL3 knockdown via the inhibition of Keap1 m6A, which regulates the p62-Keap1-Nrf2 pathway. Collectively, these findings indicate thatMETTL3-mediated m6A methylation induced by PS-NPs may represent a previously unrecognized molecular basis for placental injury.