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Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

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Kalisch-Smith, Jacinta I  ORCID logo
Ved, Nikita 
Szumska, Dorota 
Troup, Michael 


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.



Animals, Aorta, Thoracic, Biomarkers, Cardiovascular System, Cell Differentiation, Coronary Vessels, Dietary Supplements, Edema, Embryo, Mammalian, Embryonic Development, Female, Gene Expression Profiling, Gene-Environment Interaction, Green Fluorescent Proteins, Iron, Iron Deficiencies, Lymphatic Vessels, Mice, Inbred C57BL, Myocardium, Myocytes, Cardiac, Penetrance, Phenotype, Pregnancy, Signal Transduction, Stem Cells, Transgenes, Tretinoin, Mice

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Nat Commun

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Springer Science and Business Media LLC
Wellcome Trust (091911/B/10/Z, 098328, FC001117 , FC001157 , 090532/Z/09/Z, 098327 , FC001157, 098327, 107457/Z/15/Z, FC001117)
Versus Arthritis (FC001117, FC001194, FC001157)
Medical Research Council (U117562103, FC001117 , MR/S01019X/1, FC001157)
Cancer Research UK (FC001157 , FC001117)
British Heart Foundation (FS/17/55/33100, FS/17/35/32929, FS/12/63/29895, RE/18/3/34214, RE/13/1/30181)