Maternal iron deficiency perturbs embryonic cardiovascular development in mice

Nat Commun. 2021 Jun 8;12(1):3447. doi: 10.1038/s41467-021-23660-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Biomarkers
  • Green Fluorescent Proteins
  • Tretinoin
  • Iron