Format

Send to

Choose Destination
See comment in PubMed Commons below
Nature. 2015 Apr 9;520(7546):230-3. doi: 10.1038/nature14361. Epub 2015 Apr 1.

The maternal-age-associated risk of congenital heart disease is modifiable.

Author information

1
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110 USA.
2
1] Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110 USA. [2] Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110 USA.
3
1] Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110 USA. [2] Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110 USA.

Abstract

Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

Comment in

PMID:
25830876
PMCID:
PMC4393370
DOI:
10.1038/nature14361
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center