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

Abstract

Cellular development of muscle was studied in sheep fetuses at 85 days of gestation. Large and small fetuses were compared at 100, 115 and 130 days, and an additional group of large 130-day fetuses were studied following 7 days of maternal undernutrition. Myogenesis in the peroneus longus muscle was completed between 100 and 115 days of gestation, and myofibre number did not differ between small and large fetuses. The proportion of myofibre-related nuclei identified as entering S-phase of the cell cycle was 1.7% per hour in 85-day fetuses. In large fetuses, subsequent rates were relatively constant (=1.5% h ^–1 ), whereas in small fetuses cell cycle activity declined with age from 1.3 to 0.9% h ^–1 , and was 0.5 % h ^–1 in 130-day fetuses of restricted ewes. The constant rate of cell cycle activity in large fetuses was associated with an increasing estimated rate of muscle growth (peroneus longus (mg) = 0.831 ¥ 10 ^{(0.024 ¥ age [d])} , r ² = 0.98), which 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 semimembranosus muscle increased with age, large fetuses having 70% more muscle 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, therefore, with fetal nutrition during mid to late gestation.