Fetal liver hepcidin secures iron stores in utero

Kämmerer, Lara; Mohammad, Goran; Wolna, Magda; Robbins, Peter A.; Lakhal‐Littleton, Samira

doi:10.1101/799304

Cited by 5 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular mechanisms controlling iron transporter protein expression in the placenta seem to involve the concerted action of the post‐transcriptional intracellular IRP/IRE system and post‐translational regulation by fetal hepcidin. The importance of IRPs (especially IRP1 47 ) in handling placental iron has been clearly demonstrated in human 47‐49 and animal 6,50 studies. Using an almost identical model of dietary iron deficiency in pregnant mouse females, Sanghke and co‐workers observed a 50% reduction in placental Fpn expression that was very likely mediated by IRP1 6 .…”

Section: Discussionmentioning

confidence: 99%

Marginally reduced maternal hepatic and splenic ferroportin under severe nutritional iron deficiency in pregnancy maintains systemic iron supply

et al. 2021

View full text Add to dashboard Cite

The demand for iron is high in pregnancy to meet the increased requirements for erythropoiesis. Even pregnant females with initially iron‐replete stores develop iron‐deficiency anemia, due to inadequate iron absorption. In anemic females, the maternal iron supply is dedicated to maintaining iron metabolism in the fetus and placenta. Here, using a mouse model of iron deficiency in pregnancy, we show that iron recycled from senescent erythrocytes becomes a predominant source of this microelement that can be transferred to the placenta in females with depleted iron stores. Ferroportin is a key protein in the molecular machinery of cellular iron egress. We demonstrate that under iron deficiency in pregnancy, levels of ferroportin are greatly reduced in the duodenum, placenta and fetal liver, but not in maternal liver macrophages and in the spleen. Although low expression of both maternal and fetal hepcidin predicted ferroportin up‐regulation in examined locations, its final expression level was very likely correlated with tissue iron status. Our results argue that iron released into the circulation of anemic females is taken up by the placenta, as evidenced by high expression of iron importers on syncytiotrophoblasts. Then, a substantial decrease in levels of ferroportin on the basolateral side of syncytiotrophoblasts, may be responsible for the reduced transfer of iron to the fetus. As attested by the lowest decrease in iron content among analyzed tissues, some part is retained in the placenta. These findings confirm the key role played by ferroportin in tuning iron turnover in iron‐deficient pregnant mouse females and their fetuses.

show abstract

Section: Discussionmentioning

confidence: 99%

Marginally reduced maternal hepatic and splenic ferroportin under severe nutritional iron deficiency in pregnancy maintains systemic iron supply

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Moreover, the maternal hepcidin levels were further decreased by 47.73% in participants with preterm births relative to that with full-term births (Figure 2(b)), P < 0:001), presumably due to more severe iron deficiency in women with preterm 5 Disease Markers births. Emerging evidence uncovered a critical role of fetal hepcidin in the regulation of fetal iron utilization in fetal liver erythropoiesis [19]. Under this context, the hepcidin level in the cord blood was also determined, as shown in Figure 2(b).…”

Section: Changes Of Iron Regulators In Pretermmentioning

confidence: 99%

“…Iron deficiency during pregnancy has been associated with severe adverse pregnancy outcomes, including increased maternal mortality, maternal illness, perinatal death, and preterm birth [16][17][18]. Moreover, suboptimal iron availability at birth afflicts cognitive behavioral and motor skills and otherwise increases the risk of anemia in infancy [19]. The iron availability for the fetus is subject to the regulation by iron stores in the fetal liver and placenta, placental iron transportation, and maternal iron supply.…”

Section: Introductionmentioning

confidence: 99%

Disordered Maternal and Fetal Iron Metabolism Occurs in Preterm Births in Human

Liu

Zhang

et al. 2022

Disease Markers

View full text Add to dashboard Cite

Background. Increasing evidence reveals that iron deficiency during pregnancy causes adverse pregnancy outcomes. Thus far, the mechanisms underlying iron deficiency-associated preterm birth are mostly limited to animal studies. Whether the suggested mechanisms exist in human requires further investigation. The goal of this study was to characterize the iron metabolism in both the maternal side and fetal side in pregnant women with preterm birth. Methods. Serum and placenta samples were collected from 42 pregnant women divided into four groups according to the gestational week. Indicators of iron metabolism, including serum iron, serum hepcidin, placental tissue iron, ferroportin (FPN), transferrin receptor 1 (TfR1), and ferritin, were surveyed using enzyme-linked immunosorbent assays (Elisa), Western blots, and real-time quantitative polymerase chain reactions (qRT-PCR). Results. Significant reduction of maternal serum iron was observed in women with preterm birth relative to those with full-term birth, indicative of worsen iron deficiency in those mothers with preterm birth. Meanwhile, the maternal hepcidin levels were notably diminished in women with preterm birth, whereas the fetal hepcidin levels were comparable between the two groups. Moreover, the placental iron stores were remarkably reduced in the preterm group, associated with reduced concentration of TfR1 and increased FPN concentration relative to the normal controls. In other words, the ratio of placental FPN mass to TfR1 mass (PIDI index) was strikingly increased in the preterm group. Conclusions. Dysregulated iron homeostasis in both the maternal and fetal sides was implicated in preterm births, and disordered regulations in maintaining the placental iron equilibrium were also presumed to account for the compromised fetal iron supply.

show abstract

“…Fetal hepatocellular-specific knockout of hepcidin was found to increase ferroportin and decrease iron in the fetal liver. 9 Minimal, if any, effects were observed on placental ferroportin. These data support an autocrine, but no major hormonal, role for fetal hepatocellular hepcidin under physiologic conditions.…”

mentioning

confidence: 95%

“…Interestingly, blood hemoglobin concentrations were decreased in these fetuses. 9 The mechanism is unclear, but possibly hepatocellular hepcidin exerts a paracrine effect on local erythroid progenitors. Ferroportin is expressed in the erythroid lineage where it regulates iron efflux.…”

mentioning

confidence: 99%