The Placental Ferroxidase Zyklopen Is Not Essential for Iron Transport to the Fetus in Mice
The Placental Ferroxidase Zyklopen Is Not Essential for Iron Transport to the Fetus in Mice
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DOI：
10.1093/jn/nxab174
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发表时间：
2021-06-10
影响因子：
4.2
通讯作者：
Frazer, David M.
中科院分区：
文献类型：
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作者：
Helman, Sheridan L.;Wilkins, Sarah J.;Frazer, David M.
背景：亚铁氧化酶 zyklopen (Zp) 与胎盘向胎儿转移铁有关。然而，这一点的证据很大程度上是间接的。 目的：本研究旨在确定 Zp 是否对胎盘铁转移至关重要。方法：使用 8 至 12 周龄的怀孕 C57BL/6 小鼠，使用标准啮齿动物饲料建立模型，其中胎儿和胎盘的胎儿成分中的 Zp 被敲除。使用全局 Zp 敲除小鼠，整个胎盘中的 Zp 也被破坏。使用电感耦合等离子体 MS 来测量胎儿总铁，这是妊娠第 18.5 天胚胎时通过胎盘转移到胎儿的铁量的指标。通过蛋白质印迹法测量胎盘中铁转运蛋白的表达，并通过实时PCR测定胎儿肝脏中Hamp1（编码铁调节激素铁调素的基因）的表达。结果：当胎盘胎儿成分或整个胎盘中的Zp被破坏时，转移到胎儿的铁量没有变化。未观察到铁转运蛋白转铁蛋白受体 1 或铁转运蛋白表达的代偿性变化，胎儿肝脏 Hamp1 mRNA 也没有任何变化。 Hephl1 是编码 Zp 的基因，主要在胎盘的母体蜕膜中表达，而不是在输送营养的合体滋养层中表达。整个胎盘中 Zp 的破坏导致胎盘大小增加 26% (P < 0.01)。结论：我们的数据表明，Zp 对于将铁有效转移到小鼠胎儿来说并不是必需的，并且主要位于母体蜕膜中。当整个胎盘中的 Zp 被敲除时，观察到胎盘尺寸的增加表明该蛋白可能在胎盘发育中发挥作用。
Background: The ferroxidase zyklopen (Zp) has been implicated in the placental transfer of iron to the fetus. However, the evidence for this is largely circumstantial.Objectives: This study aimed to determine whether Zp is essential for placental iron transfer.Methods: A model was established using 8- to 12-wk-old pregnant C57BL/6 mice on standard rodent chow in which Zp was knocked out in the fetus and fetal components of the placenta. Zp was also disrupted in the entire placenta using global Zp knockout mice. Inductively coupled plasma MS was used to measure total fetal iron, an indicator of the amount of iron transferred by the placenta to the fetus, at embryonic day 18.5 of gestation. Iron transporter expression in the placenta was measured by Western blotting, and the expression of Hamp1, the gene encoding the iron regulatory hormone hepcidin, was determined in fetal liver by real-time PCR.Results: There was no change in the amount of iron transferred to the fetus when Zp was disrupted in either the fetal component of the placenta or the entire placenta. No compensatory changes in the expression of the iron transport proteins transferrin receptor 1 or ferroportin were observed, nor was there any change in fetal liver Hamp1 mRNA. Hephl1, the gene encoding Zp, was expressed mainly in the maternal decidua of the placenta and not in the nutrient-transporting syncytiotrophoblast. Disruption of Zp in the whole placenta resulted in a 26% increase in placental size (P < 0.01).Conclusions: Our data indicate that Zp is not essential for the efficient transfer of iron to the fetus in mice and is localized predominantly in the maternal decidua. The increase in placental size observed when Zp is knocked out in the entire placenta suggests that this protein may play a role in placental development.