Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans

Wei, Shuting; Liu, Wei; Qi, Yu; Guo, Yifan; Zhang, Shuping; Wang, Li; Zhuang, Taifeng; Zhang, Na; Liu, Sijin

doi:10.1111/bjh.17049

Cited by 10 publications

(5 citation statements)

References 53 publications

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“…ERFE regulates iron homeostasis by sequestering hepcidin inducer bone morphogenetic protein 6 (BMP6), thus lowering hepcidin levels. In nonanemic human and rodent pregnancies, serum ERFE levels are not significantly affected by pregnancy status (138). However, in mouse models of iron-restricted or iron-deficient pregnancy with ensuing anemia, maternal ERFE levels are significantly elevated (111,115).…”

Section: Inflammation and Hepcidin During Pregnancymentioning

confidence: 97%

Iron Homeostasis During Pregnancy: Maternal, Placental, and Fetal Regulatory Mechanisms

et al. 2023

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Pregnancy entails a large negative balance of iron, an essential micronutrient. During pregnancy, iron requirements increase substantially to support both maternal red blood cell expansion and the development of the placenta and fetus. As insufficient iron has long been linked to adverse pregnancy outcomes, universal iron supplementation is common practice before and during pregnancy. However, in high-resource countries with iron fortification of staple foods and increased red meat consumption, the effects of too much iron supplementation during pregnancy have become a concern because iron excess has also been linked to adverse pregnancy outcomes. In this review, we address physiologic iron homeostasis of the mother, placenta, and fetus and discuss perturbations in iron homeostasis that result in pathological pregnancy. As many mechanistic regulatory systems have been deduced from animal models, we also discuss the principles learned from these models and how these may apply to human pregnancy. Expected final online publication date for the Annual Review of Nutrition, Volume 43 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Inflammation and Hepcidin During Pregnancymentioning

confidence: 97%

Iron Homeostasis During Pregnancy: Maternal, Placental, and Fetal Regulatory Mechanisms

et al. 2023

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“…In analogy to previous findings, the maternal serum iron concentrations largely declined in the normal pregnancies from the first trimester to the third trimester ( Figure 1(c) ), P < 0.05), associated with the increased fetal iron demand [ 24 , 25 ]. And the enlarged volume of the total blood during the gestation may also dilute the iron concentrations [ 26 , 27 ]. In this study, we found that serum iron levels were lower in participants sampled in the third trimester than those sampled in the first trimester ( Figure 1(c) ), P < 0.05).…”

Section: Resultsmentioning

confidence: 99%

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

Liu

Zhang

et al. 2022

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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.

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“…In addition, ferritin-to-hepcidin or hepcidin-to-ferritin ratios were used to investigate other diseases as well [ 37 , 38 , 39 ]. Regarding hepcidin/iron and hepcidin/EPO ratios, they have not been explored in COVID-19 so far but in some other diseases [ 39 , 40 , 41 , 42 ]. Hepcidin/CRP was applied in only one study with subjects infected with SARS-CoV-2 [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Hypoxia and Inflammation on Hepcidin Concentration in Non-Anaemic COVID-19 Patients

Gugo,

Tandara,

Juricic

et al. 2024

JCM

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Background/Objectives: This study aimed to explore the influence of hypoxia, inflammation, and erythropoiesis on hepcidin and other iron status parameters in non-anaemic COVID-19 patients admitted to the emergency unit before the introduction of therapeutic interventions. Methods: Ninety-six COVID-19 patients and 47 healthy subjects were recruited. Patients were subdivided into hypoxic or normoxic groups and, after follow-up, into mild and moderate, severe or critical disease severity groups. Iron, unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP), and interleukin 6 (IL-6) were measured on automatic analysers. ELISA kits were used for hepcidin and erythropoietin (EPO) determination. We calculated total iron-binding capacity (TIBC) and ratios of hepcidin with parameters of iron metabolism (ferritin/hepcidin, hepcidin/iron), inflammation (hepcidin/CRP, hepcidin/IL-6), and erythropoietic activity (hepcidin/EPO). Results: Hepcidin, ferritin, EPO, CRP, IL-6, ferritin/hepcidin, and hepcidin/iron were increased, while UIBC, TIBC, hepcidin/CRP, and hepcidin/IL-6 were decreased in hypoxic compared to normoxic patients as well as in patients with severe or critical disease compared to those with mild and moderate COVID-19. Regarding predictive parameters of critical COVID-19 occurrence, in multivariable logistic regression analysis, a combination of EPO and ferritin/hepcidin showed very good diagnostic performances and correctly classified 88% of cases, with an AUC of 0.838 (0.749–0.906). Conclusions: The hypoxic signal in our group of patients was not strong enough to overcome the stimulating effect of inflammation on hepcidin expression. EPO and ferritin/hepcidin might help to identify on-admission COVID-19 patients at risk of developing a critical form of the disease.

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Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans

Cited by 10 publications

References 53 publications

Iron Homeostasis During Pregnancy: Maternal, Placental, and Fetal Regulatory Mechanisms

Iron Homeostasis During Pregnancy: Maternal, Placental, and Fetal Regulatory Mechanisms

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

Effects of Hypoxia and Inflammation on Hepcidin Concentration in Non-Anaemic COVID-19 Patients

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