Ferroptosis is a form of cell death associated with iron-dependent lipid peroxidation. We used a chicken embryo model to investigate if ferroptosis was implicated in the molecular mechanism underlying the potential effects of maternal exposure to iron oxide nanoparticles (IONPs) on the developing brain. One hundred and eighty fertilized eggs were randomly divided into six groups (30 eggs/group; 10 eggs/replicate). Groups I and II received maghemite (γ-Fe₂O₃) NPs (MGMNPs), while groups III and IV received magnetite (Fe₃O₄) NPs (MGTNPs). Both MGMNP and MGTNP were administrated at the concentrations of 100 and 250 ppm. One group (placebo) received saline, and the other remained untreated (control). The compounds were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebral tissue were collected on day 20 for histopathological, biochemical and gene expression analyses. Total antioxidant capacity (TAC) and malondialdehyde (MDA) increased; glutathione peroxidase (GPX) expression and activity decreased in IONPs-treated groups. Ferroptotic cells appeared in the cerebral tissue following exposure to the low dose of MGMNP and MGTNP. Oxidative stress and ferroptotic cells were more evident for MGMNP compared to MGTNP. The low dose of MGMNP and MGTNP induced more severe oxidative stress in the cerebral tissue. According to the results, maternal exposure to IONPs is associated with ferroptosis in the brain. This work could encourage future researches to investigate inhibitors of ferroptosis as a protective strategy against iron-induced cell injuries and cell death.

中文翻译：

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母体暴露于氧化铁纳米颗粒与大脑中的铁死亡有关：鸡胚模型分析

铁死亡是一种与铁依赖性脂质过氧化相关的细胞死亡形式。我们使用鸡胚模型来研究铁死亡是否与母体暴露于氧化铁纳米颗粒 (IONP) 对发育中的大脑的潜在影响的分子机制有关。180个受精卵随机分为6组（30个/组；10个/重复）。I 和 II 组接受磁赤铁矿 (γ-Fe ₂ O ₃ ) NPs (MGMNPs)，而 III 和 IV 组接受磁铁矿 (Fe ₃ O ₄) NP (MGTNP)。MGMNP 和 MGTNP 均以 100 和 250 ppm 的浓度给药。一组（安慰剂）接受生理盐水，另一组保持未治疗（对照）。仅在胚胎期的第一天通过卵内方法（0.3 ml/egg）给予化合物一次。在第 20 天收集脑组织样本用于组织病理学、生化和基因表达分析。总抗氧化能力（TAC）和丙二醛（MDA）增加；IONPs 治疗组中谷胱甘肽过氧化物酶 (GPX) 的表达和活性降低。暴露于低剂量的MGMNP和MGTNP后，铁死亡细胞出现在脑组织中。与 MGTNP 相比，MGMNP 的氧化应激和铁死亡细胞更明显。低剂量的 MGMNP 和 MGTNP 在脑组织中引起更严重的氧化应激。根据结果​​，母体暴露于 IONPs 与大脑中的铁死亡有关。这项工作可以鼓励未来的研究，以研究铁死亡抑制剂作为防止铁诱导的细胞损伤和细胞死亡的保护策略。