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Exercise was the key to fewer holes in the heart (Source: ziggy_mars/iStockphoto)

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Running off a hole in the heart

Tuesday 4th August 2015 1:45 pm

It seems that exercise can reduce the risk of congenital heart disease — if you are a mouse …

To be even more specific, a mouse that has already been bred to have a very high risk of having a hole between two of the chambers in the heart.

In humans, the heart is one of the first organs to develop in the embryo, usually within 10 weeks of conception. Not suprisingly, it’s quite complicated to turn a tube into a fully functioning pump with four chambers — two low pressure chambers (the atria) and two high pressure chambers (the ventricles).

This process is regulated by the Nkx2-5 gene.

We know that in humans, congenital heart disease is very common (about one per cent of all human births).

A common congenital heart defect is a hole between the right and left atria (atrial septal defect, or ASD) or between the right and left ventricles (ventricular septal defect, or VSD). This is your classic hole in the heart. About a tenth of these defects need surgery after birth — the rest heal themselves.

We would love to know anything that could possibly lower the risk of these defects in human babies — and so reduce both the number of defects, and the need for surgery.

One obvious starting point is the mother, who after all, provides the environment for the growing fetus. The risk for congenital heart disease includes certain infections in the mother, her genetics, environmental factors such as toxins, maternal diabetes, and finally, the age of the mother.

Using this background knowledge, scientists started with mice that had been specifically bred to have only one copy of the Nkx2-5 gene that regulates the development of the heart. Because they have only one copy of the gene, not two, these newborn mice pups have a 10 per cent risk of having a ventricular septal defect.

The chance of having a baby mouse with a VSD increases with the age of the mother mouse — but we didn’t know why. The team looked at three possible factors — the age of the ovaries, the diet of the mother mice, and the exercise taken by the mother mice.

Ventricular septal defect

Ventricular septal defect(Source: Manco Capac/Wikimedia Commons (CC BY-SA 3.0))

First, the age of the ovaries — and the eggs they carry. Half of the female mice were young (equivalent to human teenagers), while the other half were approaching mice menopause. The researchers transplanted young ovaries into the older mice, and old ovaries into the younger mice. The age of the ovaries (and eggs) had no effect. The young mice mothers (with the old ovaries) still had a lower risk. The older mice mothers (with the young ovaries) still had a higher risk. So the age of the ovaries was irrelevant.

Second factor, the diet of the mother mice. As animals get older, the metabolic rate drops, fats and sugars are metabolised differently, and the waistline expands. The researchers fed the older pregnant mice either high-fat, or normal, kibble (mouse feed). Diet made no difference.

The third and final factor was exercise. Half of the young and old mice were given running wheels in their cages, and allowed to run whenever they wanted for several weeks before becoming pregnant. The other half of the young and old mice had no running wheels — so they were the controls.


Exercise was the key to fewer holes in the heart. For the younger mice mothers, the risk was about 10 per cent — whether they ran or not. For the older running mice mothers, the risk was also about 10 per cent — but only if they exercised.

If they did not exercise, the risk of a hole in the heart jumped to about 20 per cent in the older mice mothers — they had double the number of pups with heart defects. (To make this kind of relevant to humans, a dash on the running wheel for mice is equivalent to a brisk walk for you and me.)

We still don’t know exactly what it was about the running wheel that reduced the risk for the older mice.

Furthermore, we don’t know if this effect, of the mother mouse being able to reduce the risk of a heart defect in her baby, works in humans — because last I looked, mice are not humans.

But certainly, there are many other potential health benefits for both mother and developing child when healthy pregnant women, and those contemplating pregnancy, become physically active. And there are very few disadvantages to exercise — as long as you don’t overdo it.

So running with a baby bump might make a healthy pump for the baby you ❤

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This blog first appeared on Dr Karl's Great Moments in Science

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