Publication Date:
2015-04-02
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393370/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393370/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schulkey, Claire E -- Regmi, Suk D -- Magnan, Rachel A -- Danzo, Megan T -- Luther, Herman -- Hutchinson, Alayna K -- Panzer, Adam A -- Grady, Mary M -- Wilson, David B -- Jay, Patrick Y -- P30 DK020579/DK/NIDDK NIH HHS/ -- P30 DK052574/DK/NIDDK NIH HHS/ -- P30 DK52574/DK/NIDDK NIH HHS/ -- R01 HL105857/HL/NHLBI NIH HHS/ -- T32 HL007873/HL/NHLBI NIH HHS/ -- T32HL007873/HL/NHLBI NIH HHS/ -- England -- Nature. 2015 Apr 9;520(7546):230-3. doi: 10.1038/nature14361. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110 USA. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830876" target="_blank"〉PubMed〈/a〉
Keywords:
Age of Onset
;
Aging/genetics/*physiology
;
Animals
;
Animals, Newborn
;
Diet, High-Fat
;
Female
;
Genetic Predisposition to Disease
;
Heart/physiology/physiopathology
;
Heart Diseases/*congenital/etiology/genetics/*prevention & control
;
Homeodomain Proteins/genetics
;
Hyperglycemia
;
*Maternal Age
;
Mice
;
Obesity
;
Ovary/transplantation
;
Phenotype
;
Physical Conditioning, Animal/*physiology
;
Pregnancy
;
Pregnancy, Animal/genetics/*physiology
;
Quantitative Trait Loci/genetics
;
Risk
;
Transcription Factors/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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