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The effects of diets, each with an excess of one essential amino acid, on the maintenance of pregnancy and fetal growth were investigated in rats. Rats were fed on 6% casein diet containing 5% threonine, methionine, valine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, or lysine from day 1 to day 14 or 21 of pregnancy. Excess methionine and leucine diets resulted in complete and 80% loss of fetuses, respectively. This fetal wastage was prevented by daily injection of 0.5 microgram of estrone and 4 mg of progesterone. Judging from the total food consumptions and body weight gains during pregnancy, methionine had the most severe effects, followed in order by leucine, tryptophan, valine, lysine, isoleucine, threonine, phenylalanine, and tyrosine. The weights of fetuses in the excess amino acid groups were significantly lower than those in the respective pair-fed controls. Excess aromatic amino acids caused growth retardation of fetal brain, although the levels of free tyrosine and phenylalanine in fetal brain were not high. The concentrations of free methionine and threonine were markedly elevated in the maternal plasma when these amino acids were fed in excess, but those of other amino acids were not increased appreciably by excess amounts in the diet. Changes in the maternal plasma levels of individual amino acids other than those in excess in the diet were small. On the contrary, the levels of not only the excess amino acids but also of other amino acids in fetal brains were appreciably elevated by these diets. These findings suggest that the blood-brain barrier is immature and that the synthesis of proteins in fetal brain is impaired by excess amino acids in the mothers. The importance of experiments on diets with excess of single amino acids in pregnant animals is discussed in connection with studies on inborn errors of amino acid metabolism.

The effects of excess amino acids on maintenance of pregnancy and fetal growth in rats.