Maternal Iron Supplementation during Pregnancy Affects Placental Function and Iron Status in Offspring
Abstract
Background Iron deficiency and overload during pregnancy damage to maternal and fetal health. Placenta as an organ for the transport of nutrients between mother and fetus protects fetus from the harmful effects of iron deficiency and iron overload through regulation of placental iron homeostasis. Methods To determine the effect of dietary iron supplementation during pregnancy on reproduction and the mechanism of placental iron regulation, we designed dietary high iron (HI: 344 mg/kg), medium iron (MI: 40 mg/kg), low iron (LI: 2 mg/kg) groups of pregnant female mice fed ferrous citrate 2 weeks before mating to 18.5 days of gestation. Results We find dietary iron supplementation during pregnancy effect maternal liver iron, placental iron, hemoglobin and fetal iron. Dietary iron significantly improves reproductive performance as litter weight and fetal weight. Correlation analysis suggest placental iron increased with liver iron, higher and lower liver iron is not conducive to the accumulation of fetal iron, placental iron deficiency and excess reduce litter weight. Placental transcriptome analysis revealed DEGs with the same trend in HI and LI groups compared with MI group, dietary iron may change biology process of ion transport and gland development in placenta. Granzyme may affect the placental trophoblast structure prior to delivery with iron overload uniquely. Conclusion This research highlights the importance of moderate iron supplements in pregnancy due to damage of reproduction by affecting placental function under different dose of maternal iron supplementation.
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Iron overload can lead to preeclampsia and GDM.
“Iron excess in pregnancy typically occurs following iron supplementation in non-anemic women, where iron overload can lead to preeclampsia and GDM.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [100]
Both iron deficiency and excess disrupt iron homeostasis, leading to altered erythropoiesis, placental dysfunction, oxidative stress, ferroptosis, and epigenetic modifications that can program offspring susceptibility to neurodevelopmental disorders and metabolic disease.
“Both deficiency and excess disrupt iron homeostasis, leading to altered erythropoiesis, placental dysfunction, oxidative stress, ferroptosis, and epigenetic modifications that can program offspring susceptibility to neurodevelopmental disorders and metabolic disease [99,100,101,108].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [100]
Both iron deficiency and iron overload during pregnancy pose significant risks to maternal and fetal health.
“Both iron deficiency and iron overload during pregnancy pose significant risks to maternal and fetal health [100].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [100]
Cites
Non-transferrin bound iron: a key role in iron overload and iron toxicity
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Effects of maternal iron status on placental and fetal iron homeostasis
Sangkhae, V., Fisher, A. L., Wong, S., Koenig, M. D., Tussing-Humphreys, L., Chu, A., Lelić, M., Ganz, T., & Nemeth, E. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127341 · Cited by 198 · see citing works
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Schiera, G., Macajone, G., Volpes, S., Greco, L., Di Liegro, C. M., Serio, G., Caradonna, F., & Naselli, F. (2026) · Cells · doi:10.3390/cells15040366 · Cited by 8 · see citing works
- Authors
- Guo, L., Zhang, D., Liu, S., Dong, Z., Zhou, J., Yin, Y., & Wan, D.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Wan, Dan
- Venue
- Journal of Trace Elements in Medicine and Biology
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 71
- Pages
- 126950
- ISSN
- 0946-672X (ISSN-L)
- OpenAlex
- W4210991234
- Cited by
- 12
- References
- 4
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 3
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Trace Elements in Medicine and Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China Stem Cell and Translational Research
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- maternal iron supplementation, pregnancy, placental function, fetal iron status, iron deficiency, iron overload, liver iron, litter weight, fetal weight, placental transcriptome, granzymes, trophoblast, reproductive performance
- MeSH terms
- Iron Deficiencies, Animals, Female, Iron, Placenta, Pregnancy, Iron Overload, Iron, Dietary, Dietary Supplements, Mice
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