Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy.
Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy.
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DOI：
10.1038/s41467-021-24333-z
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发表时间：
2021-06-29
影响因子：
16.6
通讯作者：
Nemeth E
中科院分区：
文献类型：
--
作者：
Fisher AL;Sangkhae V;Balušíková K;Palaskas NJ;Ganz T;Nemeth E
铁对健康的怀孕至关重要，无论母亲的铁状况如何，铁补充剂几乎都是普遍推荐的。潜在危害的一个信号是母体铁蛋白（铁储存的标志物）与不良妊娠结局风险之间的U形关联。然而，铁蛋白也由炎症诱导，并且可能在炎症或感染期间高估铁储存。在这项研究中，我们使用小鼠模型来确定母体铁负荷，炎症或它们的相互作用是否会导致不良的妊娠结局。只有母体暴露于铁过量和炎症，而不是单独的条件，导致胚胎畸形和死亡。母体铁过量在LPS诱导的急性炎症和肥胖诱导的慢性轻度炎症期间均增强胚胎损伤。不良相互作用依赖于TNFα信号传导，导致胎盘和胚胎内皮细胞凋亡，并可通过抗TNF α或抗氧化剂治疗预防。我们的研究结果提出了关于怀孕期间不加选择地补充铁的安全性的重要问题。铁在怀孕期间对胚胎和胎盘发育以及孕产妇健康至关重要。然而，在这项使用小鼠模型的研究中，作者证明了过量的母体铁会导致潜在全身炎症的妊娠不良胚胎结局。
Iron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy. Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.
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