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Cited by 3Gestational Diabetes Research and ManagementIron Metabolism and DisordersPregnancy and preeclampsia studies

Altered Placental Iron Transport and Putative Ferroptosis Pathways in Pregnancies with Excessive Gestational Weight Gain: A Prospective Cohort Study

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Ege, Serhat, Akduman, Hasan, Aşir, Ayşegül, Korak, Tuğcan, Aşir, Firat·2025·Medicine
DOI 10.1097/md.0000000000044330PMC PMC12419337
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Abstract

Excessive gestational weight gain (GWG) is associated with various adverse pregnancy outcomes, including disruption of placental function and fetal development. Iron transport through the placenta is crucial for fetal growth, and transferrin receptor 2 (TfR2) plays a key role in iron homeostasis. However, the effect of excessive GWG on placental TfR2 expression and neonatal iron parameters remains unclear. This study aimed to investigate the effect of excessive GWG on placental TfR2 expression and its association with neonatal iron levels, including cord blood serum iron levels and total iron-binding capacity. A prospective study was conducted with 90 pregnant women divided into 2 groups: 45 with normal weight gain and 45 with excessive GWG. Placental TfR2 expression was assessed via immunohistochemistry, whereas neonatal iron parameters were analyzed in umbilical cord blood using biochemical assays. Additionally, in silico analyses were performed to explore the molecular pathways linking TfR2 expression and iron homeostasis. Placental TfR2 expression was significantly increased in the excessive GWG group compared to controls, with high immunoreactivity observed in the trophoblastic layer, capillaries, and villous connective tissue. Neonates from mothers with excessive GWG had significantly higher cord blood serum iron levels ( P = .025) and lower total iron-binding capacity levels ( P = .017). Bioinformatics analysis revealed that TfR2 is involved in iron homeostasis regulation, and ferroptosis emerged as a potentially relevant pathway. Excessive GWG may be associated with altered placental iron transport and increased TfR2 expression, which could contribute to iron overload and involvement of ferroptosis-related pathways. However, the lack of direct ferroptosis markers such as GPX4, ACSL4, reactive oxygen species levels, or cell-death assays limits mechanistic confirmation. Further studies are required to validate the role of ferroptosis in this context.

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  • Excessive weight gain leads to overexpression of TfR2, resulting in excessive iron absorption and subsequent iron overload within trophoblast cells, accompanied by increased lipid peroxidation, oxidative damage, inflammation, and placental dysfunction, potentially leading to preeclampsia and GDM.

    “A study by Ege et al. (2025) demonstrated that excessive weight gain leads to the overexpression of TfR2, resulting in excessive iron absorption and subsequent iron overload within trophoblast cells [105].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [105]

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Cited by

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Authors
Ege, S., Akduman, H., Aşir, A., Korak, T., & Aşir, F.
Affiliations
  • Dicle University (TR)
  • Ankara Etlik City Hospital (TR)
  • Division of Pediatrics, Gazi Yaşargil Training and Research Hospital, Diyarbakir, Turkey
  • Kocaeli Üniversitesi (TR)
  • Department of Histology and Embryology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey.
ORCID
Venue
Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2025-09-05
Volume
104
Issue
36
Pages
e44330
ISSN
  • 0025-7974 (ISSN-L)
  • 1536-5964
DOI
10.1097/md.0000000000044330
PMC
PMC12419337
OpenAlex
W4414079853
Cited by
3
References
2
Citations by year
2026: 3
FWCI
3.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Medicine (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • Kocaeli Üniversitesi - AVESİS (submittedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
excessive gestational weight gain, placental iron transport, transferrin receptor 2, ferroptosis, neonatal iron status, total iron binding capacity, trophoblast, iron overload
MeSH terms
Gestational Weight Gain, Ferroptosis, Adult, Female, Fetal Blood, Humans, Infant, Newborn, Iron, Placenta, Pregnancy, Pregnancy Complications, Prospective Studies, Receptors, Transferrin

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