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Maternal iron deficiency perturbs embryonic cardiovascular development in mice

Published version
Peer-reviewed

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Authors

Kalisch-Smith, Jacinta I.  ORCID logo  https://orcid.org/0000-0002-5071-3805
Ved, Nikita 
Szumska, Dorota 
Troup, Michael 

Abstract

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.

Description

Funder: Novo Nordisk; doi: https://doi.org/10.13039/501100004191


Funder: National Heart Foundation of Australia (Heart Foundation); doi: https://doi.org/10.13039/501100001030


Funder: NSW Health; doi: https://doi.org/10.13039/501100009287


Funder: Oxford University | John Fell Fund, University of Oxford (John Fell OUP Research Fund); doi: https://doi.org/10.13039/501100004789


Funder: The Federated Foundation

Keywords

Article, /631/136/1425, /631/136/2086, /692/308/1426, /692/499, /64, /64/60, /82/80, /96/35, /82/1, /13/51, /14/1, /14/5, /14/19, /14/32, /14, /14/63, /38/1, /38/39, /38/91, /59/57, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

12

Publisher

Nature Publishing Group UK
Sponsorship
British Heart Foundation (BHF) (RE/18/3/34214, FS/12/63/29895, FS/17/35/32929, FS/17/55/33100, RE/13/1/30181, RE/18/3/34214)
Wellcome Trust (Wellcome) (098328, 098328)
RCUK | Medical Research Council (MRC) (MR/S01019X/1)