Materno-fetal iron transfer and the emerging role of ferroptosis pathways

Zaugg, Jonas; Solenthaler, Fabia; Albrecht, Christiane

doi:10.1016/j.bcp.2022.115141

Cited by 21 publications

(15 citation statements)

References 228 publications

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“…The Feline Leukemia Virus Subgroup C has been identified as having roles in cellular heme transport and in the control of intracellular heme content as heme synthesis increases to support erythrocyte differentiation [ 51 ]. Free heme may be exported by the Feline Leukemia Virus Subgroup C receptor 1 or 2 (FLVCR1/2) or converted into inorganic Fe by heme oxygenase [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Are Antisense Long Non-Coding RNA Related to COVID-19?

et al. 2022

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Fighting external pathogens relies on the tight regulation of the gene expression of the immune system. Ferroptosis, which is a distinct form of programmed cell death driven by iron, is involved in the enhancement of follicular helper T cell function during infection. The regulation of RNA is a key step in final gene expression. The present study aimed to identify the expression level of antisense lncRNAs (A2M-AS1, DBH-AS1, FLVCR1-DT, and NCBP2AS2-1) and FLVCR1 in COVID-19 patients and its relation to the severity of the disease. COVID-19 patients as well as age and gender-matched healthy controls were enrolled in this study. The expression level of the antisense lncRNAs was measured by RT-PCR. Results revealed the decreased expression of A2M-AS1 and FLVCR1 in COVID-19 patients. Additionally, they showed the increased expression of DBH-AS1, FLVCR1-DT, and NCBP2AS2. Both FLVCR1-DT and NCBP2AS2 showed a positive correlation with interleukin-6 (IL-6). DBH-AS1 and FLVCR1-DT had a significant association with mortality, complications, and mechanical ventilation. A significant negative correlation was found between A2M-AS1 and NCBP2AS2-1 and between FLVCR1 and FLVCR1-DT. The study confirmed that the expression level of the antisense lncRNAs was deregulated in COVID-19 patients and correlated with the severity of COVID-19, and that it may have possible roles in the pathogenesis of this disease.

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Section: Discussionmentioning

confidence: 99%

Are Antisense Long Non-Coding RNA Related to COVID-19?

et al. 2022

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“…Furthermore, Zrt- and Irt-like protein 8 (ZIP8) and Zrt- and Irt-like protein 14 (ZIP14), both of which play a roles in exporting iron from placental endosomal into the cytosol, are found at high levels in human placenta ( Jenkitkasemwong et al, 2012 ). Three reviews described details on the role of iron and ferroptosis in the placenta ( Ng et al, 2019 ; Beharier et al, 2021 ; Zaugg et al, 2022 ). Finally, decreased GPX4 levels have been associated with human placental dysfunction ( Zhang et al, 2020 ).…”

Section: Role Of Ferroptosis In Pregnancy Related Diseasesmentioning

confidence: 99%

“…GDM is associated with long-lasting complications in the short and long term, such as macrosomia ( Song et al, 2022 ), dystocia ( Crowther et al, 2022 ), childhood obesity in the child ( Choi et al, 2022 ), recurrence of GDM ( Giuliani et al, 2022 ), developing type 2 diabetes ( Vounzoulaki et al, 2020 ) and cardiovascular disease in the mother ( Christensen et al, 2022 ). Emerging evidence suggests ferroptosis contributes to the pathogenesis of GDM ( Han et al, 2020 ; Gautam et al, 2021 ; Zhang et al, 2022c ; Hu et al, 2022 ; Zaugg et al, 2022 ). The insulin sensitivity shifts depending on the requirements of pregnancy, which is an important metabolic adaptation during healthy pregnancy ( Di Cianni et al, 2003 ).…”

Section: Role Of Ferroptosis In Pregnancy Related Diseasesmentioning

confidence: 99%

“…Iron overload, leading to oxidative stress damage, could promote the pathogenesis of GDM ( Gautam et al, 2021 ; Zhang et al, 2022c ; Zaugg et al, 2022 ). As reported, both elevated plasma ferritin concentrations and iron supplementation in pregnant women having adequate iron stores are risk factors of GDM ( Zhang et al, 2021 ).…”

Section: Role Of Ferroptosis In Pregnancy Related Diseasesmentioning

confidence: 99%

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Role of ferroptosis in pregnancy related diseases and its therapeutic potential

Zhang²,

Wang³

et al. 2023

Front. Cell Dev. Biol.

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Ferroptosis is a form of regulated cell death characterized by iron overload, overwhelming lipid peroxidation, and disruption of antioxidant systems. Emerging evidence suggests that ferroptosis is associated with pregnancy related diseases, such as spontaneous abortion, pre-eclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and spontaneous preterm birth. According to these findings, inhibiting ferroptosis might be a potential option to treat pregnancy related diseases. This review summarizes the mechanisms and advances of ferroptosis, the pathogenic role of ferroptosis in pregnancy related diseases and the potential medicines for its treatment.

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“…A mechanism by which maternal metabolic diseases during pregnancy may impact the developing child could involve altered iron homeostasis [ 16 ]. Iron requirements progressively increase to meet the demand for erythropoiesis and iron-dependent enzymes during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Obesogenic diet in pregnancy disrupts placental iron handling and ferroptosis and stress signalling in association with fetal growth alterations

Zaugg,

Lopez-Tello,

Musial

et al. 2024

Cell. Mol. Life Sci.

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Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth. Female mice were fed a standard chow or high fat, high sugar (HFHS) diet during pregnancy and outcomes were measured at day (d)16 or d19 of pregnancy. In HFHS-fed mice, maternal hepcidin was reduced and iron status maintained (tissue iron levels) at both d16 and d19. However, fetal weight, placental iron transfer capacity, iron deposition, TFR1 expression and ERK2-mediated signalling were reduced and oxidative damage-related lipofuscin accumulation in the placenta was increased in HFHS-fed mice. At d19, whilst TFR1 remained decreased, fetal weight was normal and placental weight, iron content and iron transporter genes (Dmt1, Zip14, and Fpn1) were reduced in HFHS-fed mice. Furthermore, there was stress kinase activation (increased phosphorylated p38MAPK, total ERK and JNK) in the placenta from HFHS-fed mice at d19. In summary, a maternal HFHS diet during pregnancy impacts fetal growth trajectory in association with changes in placental iron handling, ferroptosis and stress signalling. Downregulation of placental iron transporters in HFHS mice may protect the fetus from excessive oxidative iron. These findings suggest a role for alterations in placental iron homeostasis in determining perinatal outcomes of pregnancies associated with GDM and/or maternal obesity. Graphical Abstract

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Materno-fetal iron transfer and the emerging role of ferroptosis pathways

Cited by 21 publications

References 228 publications

Are Antisense Long Non-Coding RNA Related to COVID-19?

Are Antisense Long Non-Coding RNA Related to COVID-19?

Role of ferroptosis in pregnancy related diseases and its therapeutic potential

Obesogenic diet in pregnancy disrupts placental iron handling and ferroptosis and stress signalling in association with fetal growth alterations

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