Effects of maternal immunisation against myostatin on post-natal growth and skeletal muscle mass of offspring in mice

The objective of this study was to examine the effect of maternal immunisation against myostatin, a potent negative regulator of skeletal muscle growth, on the skeletal muscle growth of offspring in mice. Twenty female mice were divided into four groups and immunised against keyhole limpet haemocyanin (control) or recombinant mature myostatin (rMyo), or two different myostatin synthetic peptides conjugated to keyhole limpet haemocyanin (Myo1 and Myo2). Offspring were sacrificed at 8 weeks of age to measure carcass, muscle and fat masses. Sera collected from 3-day-old neonates of the rMyo, Myo1 and Myo2 groups showed titres against myostatin, confirming the maternal transfer of anti-myostatin antibodies to offspring. No significant effects of immunisation on offspring weight were observed. The offspring of the Myo2 group, but not the rMyo and Myo1 groups, had significantly heavier gastrocnemius and triceps muscle mass than those of the control (p<0.01). All IgGs of the three treatment groups showed affinity to mature myostatin monomer in Western blot analysis, but none of the IgGs showed affinity to myostatin dimer. The IgGs of all the treatment groups failed to suppress the biological activity of myostatin in an A204 cell-based pGL3 (CAGA)12-luciferase reporter system, demonstrating that the increase in skeletal muscle mass observed in the offspring of the Myo2 group might not result from the inhibition of myostatin's biological activity by the anti-Myo2 antibodies. In conclusion, the results of this study suggest that antigen preparation may affect the responsiveness of skeletal muscle growth of offspring when maternal immunisation against myostatin is used as a potential tool to improve skeletal muscle growth of offspring.