Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies: A retrospective study

Masoumi, Zahra; Hansson, Lucas R.; Hansson, Eva Ekvall; Ahlm, Evelina; Mezey, Éva; Erlandsson, Lena; Hansson, Stefan R.

doi:10.1016/j.placenta.2023.01.008

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…In this study, we report that an increased accumulation of extracellular ferric iron and TFRC can be observed in the placentas of women with LO-PE. Contrary to our results, Masoumi et al [64] found that the placentas of women with EO-PE (n = 6) presented increased iron deposits evidenced by this technique; but no significant changes were found between LO-PE (n = 10) and healthy pregnant women (n = 10). In parallel, TFRC was shown to be slightly decreased in both types of preeclampsia.…”

Section: Discussioncontrasting

confidence: 99%

“…Perls' Prussian Blue staining is responsible for detecting the iron in a ferric state. Increased iron deposits in the placenta of women with different diseases through the application of Perls' Prussian Blue staining have been demonstrated in past works [64,65]. Similarly, an altered expression of TFRC seems to be broadly accepted as an important marker of ferroptosis [66].…”

Section: Discussionmentioning

confidence: 91%

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Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia

Ortega,

Garcia-Puente,

Fraile-Martinez

et al. 2024

Antioxidants

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Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe3+) was observed in placenta samples stained with Perls’ Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 91%

Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia

Ortega,

Garcia-Puente,

Fraile-Martinez

et al. 2024

Antioxidants

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“…Iron absorption increases during pregnancy, and little is known about the mechanisms regulating maternal iron levels and transfers through the placenta. In the trophoblasts decreased levels of erythroferrone, a hormone that increases plasma iron availability by suppressing hepcidin to facilitate hemoglobin and erythropoiesis was found in early-onset PE [8]. However, the maternal plasma erythroferrone levels were increased in PE.…”

Section: Introductionmentioning

confidence: 99%

Increased ferroptosis in leukocytes from preeclamptic women involving the long non‐coding taurine upregulated gene 1 (TUG1)

Lekva,

Michelsen,

Roland

et al. 2023

J Intern Med

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BackgroundFerroptosis plays a key role in placental development and physiology, and abnormal ferroptosis has been implicated in trophoblast injury leading to preeclampsia (PE). We hypothesize that leukocytes isolated from PE exhibit increased ferroptosis and that extracellular vesicles contain long non‐coding (lnc) RNA/mRNAs that modulate oxidative stress and iron toxicity in vascular endothelial cells.MethodsWe measured the expression of key regulators of ferroptosis in leukocytes and extracellular vesicles as well as circulating biomarkers of iron homeostasis and oxidative stress in plasma from women with/without PE at different timepoints during pregnancy. For markers that were dysregulated, we assessed their temporal correlation with established markers of disease activity and marker of endothelial activation. For markers dysregulated in early pregnancy, we assessed their ability to predict the development of PE.ResultsWe found decreased lncRNA/mRNAs in leukocytes, but not extracellular vesicles, in PE that may modulate oxidative stress and iron toxicity. This decrease in anti‐ferroptotic markers does not appear to be related to maternal disease activity or plasma oxidative stress status but rather to attenuated anti‐inflammatory expression in these cells. Circulating ferritin was elevated in PE, supporting the hypothesis that PE represents a disbalance in iron homeostasis. Low lncRNA taurine upregulated gene 1 RNA levels in leukocytes at 22–24 weeks were strongly associated with the development of PE.ConclusionsOur findings suggest that maternal leukocytes in PE show decreased anti‐ferroptotic activity that correlates with anti‐inflammatory expression. Moreover, some of these changes in ferroptotic activity appear to precede the development of PE.

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Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples

Delaney,

Barad,

Castillo

et al. 2023

The Journal of Nutrition

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Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies: A retrospective study

Cited by 3 publications

References 43 publications

Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia

Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia

Increased ferroptosis in leukocytes from preeclamptic women involving the long non‐coding taurine upregulated gene 1 (TUG1)

Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples

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