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The genetic mechanism for effect of maternal protein deficiency on muscle problems in male offspring identified

Posted:  Tuesday, September 29, 2015

Pregnant women require an additional 25 grams of protein per day to support the baby’s growth and development. Studies have shown that inadequate consumption of protein by the mother during pregnancy could lead to chronic health problems in the offspring. Now, a new research has found that protein deficiency during pregnancy could lead to muscle problems in mothers and their male offspring. The researchers have identified the genetic mechanism for this association.

The study, published in the British Journal of Nutrition, provided pregnant rats with either a low protein diet (8 or 9 grams of protein) or a control diet (18 to 20 grams of protein). The researchers observed that mothers on the low protein diet gained significantly less weight and that their pups were smaller at birth compared with the controls. The serum levels of key amino acids in these mothers also showed changes suggesting disturbances in protein metabolism. A major finding was atrophy in the skeletal muscle of the mother rats characterised by smaller fibre size, greater variation in fibre diameter and split fibres.

The researchers found 2 ways by which inadequate protein during pregnancy caused cell destruction or autophagy and wasting or atrophy of the skeletal muscle.

•   Protein deficiency seemed to activate the amino acid response (AAR) pathway responsible for cell destruction.

•   Low protein diet seemed to activate the ATF4 gene, an important regulatory protein in the AAR pathway. ATF4 seemed to be involved in muscle dystrophy and autophagy.

Autophagy is a survival mechanism wherein the cells eliminate unnecessary or dysfunctional components for homeostasis. Follow up studies found that the autophagy genes and AAR genes remained activated in the skeletal muscles of the male pups.

Incredibly, the researchers found that the maternal genetic changes are transferred through the placenta and ‘memorised’ by the foetal skeletal muscles resulting in low birth weight and stunting in male progeny. "This is the link we've been seeking for years, which shows transduction from the mom through the placenta to the child. However, the cell autophagy is activated in the skeletal muscles of the male offspring only, so there is gender specificity. Apparently the female offspring have more resistance to low-protein exposure during gestation and to cell autophagy," said the researchers.

Although the study findings were reported in rats, implications of protein deficiency in humans are similar. This accentuates the importance of a balanced maternal diet for good pregnancy outcomes. Detecting protein insufficiency early on in pregnancy can help avert this condition through dietary interventions.

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