Intrauterine growth retardation is associated with reduced cell cycle activity, but not myofibre number, in ovine fetal muscle

Cellular development of muscle was studied in sheep fetuses at 85 days of g estation. Large and small fetuses were compared at 100, 115 and 130 days, a nd an additional group of large 130-day fetuses were studied following 7 da ys of maternal undernutrition. Myogenesis in the peroneus longus muscle was completed between 100 and 115 days of gestation, and myofibre number did n ot differ between small and large fetuses. The proportion of myofibre-relat ed nuclei identified as entering S-phase of the cell cycle was 1.7% per hou r in 85-day fetuses. In large fetuses, subsequent rates were relatively con stant (approximate to 1.5% h(-1)), whereas in small fetuses cell cycle acti vity declined with age from 1.3 to 0.9% h(-1), and was 0.5 % h(-1) in 130-d ay fetuses of restricted ewes. The constant rate of cell cycle activity in large fetuses was associated with an increasing estimated rate of muscle gr owth (peroneus longus (mg) = 0.831 x 10((0.024 x age [d])), r(2) = 0.98), w hich contrasted with slow and relatively constant muscle accretion in small fetuses (8.4 mg day(-1)), and slower muscle accretion at 130 days in large fetuses from restricted ewes. Differences in DNA and RNA content in the se mimembranosus muscle increased with age, large fetuses having 70% more musc le DNA, 108% more muscle RNA and 104% larger muscles than small fetuses at 130 days (all P<0.001). The results demonstrate that myonuclei accumulation , but not myofibre number, is associated with fetal growth in sheep and the refore, with fetal nutrition during mid to late gestation.