Fetal hepatic and placental amino acid metabolism : experimental studies in late ovine gestation

For a long time, the study of the metabolism of nutrients by the placenta attracted much less attention than that by the fetus. This scant interest was probably due to the commonly held view of the placenta as an organ with minimal metabolic needs, serving only as a means of transport between the maternal and fetal circulations. This concept changed when it was demonstrated that in late ovine gestation only about half of the oxygen taken up from the uterine circulation is actually delivered to the fetus whereas the other half is used by the placenta itself, which implies a high metabolic rate approximately equal to that of the brain. Further quantitative in vivo studies on net substrate fluxes across both fetal and maternal circulations of the uteroplacental unit demonstrated that placental metabolism plays a significant role in the nutritional demands of pregnancy. In obstetrics the main focus of scientific interest has been on the significance of reduced uteroplacental and lUllbilical perfusion with impaired oxygenation and uptake of nutrients as the pathophysiological mechanism of fetal growth restriction. But in smallfor- gestational age (SGA) fetuses, not only total aminonitrogen levels are reduced, there are also marked differences between adequate-for-gestational age (AGA) and SGA fetuses with respect to fetal concentrations of leucine, isoleucine and valine. A possible role for placental amino acid metabolism in fetal growth restriction is apparent from in vivo experiments in ovine gestation with restriction of fetal growth induced by heat-stress. These studies showed a significantly reduced uterine uptake of essential amino acids such as threonine and leucine by the placenta expressed per gram of placenta. This finding is supported by the observation of a significantly reduced amino acid transport activity by microvillous vesicles from placentas obtained from patients with fetal growth restriction.

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