Muscle development during fetal growth in mammals is impaired by abnormal regulation of a gene, a study led by scientists at the Roslin Institute shows.

Levels of the gene, known as KLB, are higher than normal in fetuses that experience impaired growth in the womb, scientists have found.

Working together with a hormone called FGF21, the gene suppresses the activity of a protein, known as mTOR, which is crucial to normal cell growth, survival and metabolism. This has a negative effect on muscle-forming cells and causes a reduction in muscle growth, the study found.

These effects of KLB on muscle cells occur in both pigs and humans, suggesting the gene plays a vital role in regulating muscle development and function in mammals.

Findings from the study could inform strategies to manage the condition, known as intrauterine growth restriction, which causes life-long ill health in animals and people.  

The outcomes could also be applied to increase sustainability of pig production by reducing the effects of this gene, which results in accumulation of fat rather than muscle in affected animals and thus reduces profits to pig producers.

Scientists analyzed the genetic code of litters of piglets and compared gene activity in fetuses affected by IUGR with healthy fetuses from the same litters.

They also tested whether KLB mediated the effects of IUGR on muscle development, given that the gene was present in high levels in IUGR piglets, and found that it is linked with reduced activity and growth of muscle cells.

The findings, which are published in the Journal of Physiology, may be significant for humans, experiments with cell cultures suggest, but further research is needed to establish the full effects of IUGR on early muscle development in people.

"Foetal growth restriction is an important cause of newborn disease and death in humans and domestic animals, particularly in pigs," says Xavier Donadeu with the Roslin Institute. "Our results help understand this condition, informing the next steps towards improving life-long welfare in affected individuals. They could also help inform methods to ensure health of pig herds."

The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh's Royal School of Veterinary Studies.

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