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Updated: Nov 2, 2025
Quantitating Iron Transport Across the Mouse Placenta In Vivo Using Nonradioactive Iron Isotopes
Published on: May 10, 2022
Maternal iron deficiency perturbs embryonic cardiovascular development in mice
Jacinta I Kalisch-Smith1, Nikita Ved1, Dorota Szumska1
1Department of Physiology, Anatomy and Genetics, BHF Centre of Research Excellence, University of Oxford, Oxford, UK.
Insights
Maternal iron deficiency in mice causes congenital heart defects (CHD) in offspring, likely due to increased retinoic acid signaling. Early iron supplementation can prevent these cardiovascular defects.
Area of Science:
- Developmental biology
- Teratology
- Genetics
Background:
- Congenital heart disease (CHD) is a common birth defect, with unknown causes in many cases.
- In utero exposure to environmental teratogens is a suspected cause for idiopathic CHD.
- Gene-environment interactions may influence CHD susceptibility.
Purpose of the Study:
- To identify potential environmental teratogens causing CHD.
- To investigate the role of maternal iron deficiency (ID) in causing cardiovascular defects.
- To explore the interaction between maternal ID and genetic predisposition in CHD.
Main Methods:
- Induction of maternal ID in a mouse model.
- Assessment of cardiovascular and craniofacial development in offspring.
- Analysis of retinoic acid signaling pathways.
- Evaluation of maternal iron supplementation efficacy.
- Assessment of maternal ID in a mouse model of Down syndrome.
Main Results:
- Maternal ID in mice leads to severe cardiovascular defects in offspring.
- These defects are associated with increased retinoic acid signaling in embryos.
- Iron administration during early pregnancy prevents the observed defects.
- Maternal ID exacerbates heart and craniofacial defects in a mouse model of Down syndrome.
Conclusions:
- Maternal iron deficiency is identified as a potential teratogen causing CHD in mice.
- Increased retinoic acid signaling is a likely mechanism for ID-induced cardiovascular defects.
- Maternal ID can worsen CHD in the context of genetic predisposition.
- Further research is needed to determine the clinical relevance for human pregnancies.
Abstract:
Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.
