Division of Obstetrics and Gynecology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Division of Obstetrics and Gynecology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Placenta. 2023 Mar 3;133:10-18. doi: 10.1016/j.placenta.2023.01.008. Epub 2023 Jan 20.
Preeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and transfer through the placenta in normal and complicated pregnancies.
In this retrospective study, we investigated the regulation of maternal and placental iron availability and storage, in normotensive and pregnancies complicated by early- or late-onset PE. Methods used were analysis of clinical records, ELISA analysis on plasma samples, immunofluorescent and Prussian Blue analysis on placenta biopsies.
Focusing on erythroferrone (ERFE) as a new marker and hormonal regulator of iron, our results demonstrated altered maternal ERFE levels in PE. We are the first to report the expression of ERFE in trophoblasts and indicate its lower levels in early-onset PE placentas. These changes were associated with lower placental transferrin receptor 1 (TfR1) in syncytiotrophoblasts in both early- and late-onset PE. In addition, maternal plasma ERFE levels were elevated in both early- and late-onset PE and hepcidin levels reduced in early-onset PE. Unaltered maternal plasma IL-6 levels suggest mechanism other than inflammation being involved in altered iron regulation in PE pregnancy.
Our data supports a deregulation in maternal iron bioavailability in early- and late-onset PE vs normotensive pregnancies. The exact role of placental ERFE in regulating maternal-placental-fetal iron transport axis requires further investigation.
子痫前期（PE）是一种与母体高血压和胎盘功能障碍相关的妊娠相关疾病。怀孕期间一种重要的微量营养素是铁，它在细胞功能中很重要。虽然怀孕期间铁的吸收增加，但对于调节母体铁水平和正常及复杂妊娠中通过胎盘转移的确切机制知之甚少。
在这项回顾性研究中，我们研究了正常妊娠和早发性或晚发性 PE 妊娠中母体和胎盘铁的可用性和储存的调节。使用的方法是分析临床记录、血浆样本的 ELISA 分析、胎盘活检的免疫荧光和普鲁士蓝分析。
我们专注于作为新标志物和铁激素调节剂的红细胞生成素（ERFE），结果表明 PE 中母体 ERFE 水平发生改变。我们是第一个报告 ERFE 在滋养细胞中表达并表明其在早发性 PE 胎盘中的水平较低的人。这些变化与早发性和晚发性 PE 中合体滋养细胞中的胎盘转铁蛋白受体 1（TfR1）水平降低有关。此外，早发性和晚发性 PE 中母体血浆 ERFE 水平升高，早发性 PE 中铁调素水平降低。未改变的母体血浆 IL-6 水平表明，在 PE 妊娠中，改变铁调节的机制除了炎症之外还有其他机制。
我们的数据支持早发性和晚发性 PE 与正常妊娠相比，母体铁生物利用度的失调。胎盘 ERFE 在调节母体-胎盘-胎儿铁转运轴中的确切作用需要进一步研究。
