The study, published in the Journal of Endocrinology, tested how stress signals from malnutrition – known as glucocorticoids – affect the growth of foetal muscles using a rat model.
The authors behind the work say the findings suggest that maternal malnutrition can cause increased stress signalling, and that this leads to compromised muscle development that cannot be reversed over time.
"It is important to know how muscles are affected in the foetus because we need muscles to breathe, to eat and swallow and to move," said senior researcher Dr Marta Fiorotto from the USDA/ Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital. "If those muscles are compromised in any way during foetal development, those functions are also likely to be compromised in the new-born baby and affect his or her growth."
While poor maternal diet has long been associated with low birth weight and long-term health risks, Fiorotto and her team aimed to test whether it is a lack of proper nutrition during pregnancy itself or associated exposure to glucocorticoids that affects foetal growth – and to find the specific physiological impact on muscle development.
They found that malnutrition leads to impaired development of foetal muscles – and that the blacked development could result in long-term health issues.
"Maternal stress, due to malnutrition or other causes that increase the exposure of her foetus to glucocorticoids, can significantly affect the growth of foetal muscles," said study co-author Dr Ganga Gokulakrishnan from Texas Children's Hospital.
"You can think of a muscle as a bundle of uncooked spaghetti; each spaghetti is a fibre - a single muscular cell - with many nuclei in a matrix of protein," explained Gokulakrishnan – who noted that the number of fibres in any muscle is already determined at birth and cannot be increased throughout life.
She added that after birth can only grow by either adding both more protein or more nuclei (known as satellite cells) to existing fibres.
Previous studies in rats have shown that exposing fetuses to glucocorticoids impairs muscle growth, and that this is due in part to reduced protein production.
In this study, the team examined the effect of glucocorticoids on the addition of nuclei to the fibers by satellite cells during early development.
"We were surprised at the magnitude of impairment we observed in the replication of satellite cells in the muscles of fetal rats exposed to glucocorticoids," said Gokulakrishnan. "Taking all the results together, we found that the effect of glucocorticoids on fetal muscle growth is quite complex; it depends on the duration, the level of glucocorticoids and the time during pregnancy when it occurs."
The team reported that whenstress is mild, such as when the mother's food intake is around 85% of normal, protein deposition in muscles of the foetus is affected ‘quite remarkably.’ However, this mild restriction in food intake does not affect the accumulation of nuclei.
"However, our results from the current study indicate that treating rats with a dose of glucocorticoids that mimics more severe food restriction affects the reserve of satellite cells, the accumulation of nuclei in the fibres, and therefore, muscle growth," Gokulakrishnan revealed.
Fiorotto noted that because the developmental issues affect muscle stem cells, it is possible that these negative effects could have life-long consequences.
“This is another example that illustrates how the health of future generations starts with the health of the mother,” she said.
Source: Journal of Endocrinology
Published online ahead of print, doi: 10.1530/JOE-16-0372
“Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat”
Authors: G. Gokulakrishnan, et al