Effect of excess phenylacetate diet during pregnancy on fetal brain growth in rats

The effects of phenylacetate (PA) on fetal brain growth were examined in pregnant rats receiving a 20% casein diet with 1.0, 1.5, 2.0 or 2.5% PA. Control rats were fed the 20% casein diet ad libitum or restricted to daily consumption of 9 and 6 g. In experimental groups of rats total food intake during pregnancy decreased, however the decrease was not so large as we had expected. By plotting the fetal brain weight (Y, mg) against maternal food intake (X, g/21 days) in control groups the following hyperbolic regression equation was obtained: Y = -4243/X + 124.6 (n: 18, r = 0.80, p < 0.001). Similar plots for excess PA rats fell below this line, indicating that prenatal fetal brain growth was impaired by an excess in PA per se specifically, as well as by decreased food intake nonspecifically. Administering the excess PA diets resulted in decreases in total RNA, total protein and RNA/DNA ratio in the fetal brain, whereas total DNA was unchanged, showing the impairment of protein synthesis, not proliferation. No remarkable changes in concentration and pattern of free amino acids in maternal plasma in excess PA groups were observed. Using a relation between total food intake during pregnancy and fetal brain weight, the extent of specific and nonspecific effects of excess PA and phenylalanine on brain growth was compared.