The effects of intrauterine growth retardation on synaptogenesis and mitochondrial formation in the cerebral and cerebellar cortices of fetal sheep.

In an experimental model of growth retardation which involves the reduction of placental mass in sheep, we have investigated the effects of intrauterine deprivation on synaptogenesis, synaptic ultrastructure and mitochondrial formation in the cerebral and cerebellar cortices of fetal sheep (140 days gestation). In the growth-retarded fetus, the numerical density of synapses in layer I of the visual cortex was reduced by 17% (P less than 0.05) compared with controls but there was no detectable difference between the two groups in the density of parallel fibre-Purkinje cell synapses in the molecular layer of the cerebellum. The length and curvature of the postsynaptic density at synapses in both regions were not affected in growth retardation but the synaptic cleft was 13% wider in the cerebellum (P less than 0.05) in growth retardation compared with controls. The number of mitochondrial profiles per unit area of neuropil in the visual cortex was increased by 20% (P less than 0.01) in growth retardation and the electron density of the inner matrix increased but the average profile area was not affected. These findings show that intrauterine growth retardation affects some aspects of synaptic development in the cerebellum and the visual cortex. The increase in the number of mitochondrial profiles in the visual cortex of growth-retarded fetuses might be an attempt by the cortical neurons to compensate for the reduced efficiency of aerobic metabolism in individual mitochondria.