The influence of undernutrition during gestation on skeletal muscle cellularity and on the expression of genes that control muscle growth

Abstract

We examined the effects of two levels of gestational undernutrition (50% and 40% ofad libitum) on postnatal growth rate, skeletal muscle cellularity and the expression of genes that control muscle growth, in the offspring at weaning. The results showed that the rat pups born to mothers fed the 50% diet during gestation and a control diet during lactation had an increased postnatal growth rate compared with the pups fed the more restricted diet (40% ofad libitum). Surprisingly, the growth rate of the control group (ad libitum) was intermediate between the 50% and 40% groups. The restricted diets did not alter the number of muscle fibres in the semitendinosus muscle of the offspring but the number of muscle nuclei was reduced by 16% in the 40% group compared with the control group. In the 50% group, the lightest pups at birth (L) had elevated muscle insulin-like growth factor (IGF)-1, IGF binding protein (BP)-5 and proliferating cell nuclear antigen (PCNA) mRNA compared with the L pups from both the control and 40% groups. The heaviest pups at birth (H) in the 50% group had increased levels of IGFBP-4, PCNA and M-cadherin mRNA compared with both the control and 40% groups. Levels of IGF-1 receptor, myostatin and MyoD mRNA did not correlate with postnatal growth. Both H and L pups from the 40% group had reduced muscle IGF-1 mRNA but all other transcripts examined were similar to control levels. The results suggest that the increased postnatal growth rate, which accompanied milder fetal undernutrition (50%), may be due to a more active local muscle IGF system and increased muscle-cell proliferation.