Project description:Decreased fetal nutrient delivery is a major cause of developmental neuropathology. Although intrauterine growth restriction spares fetal brain weight, we hypothesized that frontal cortices of fetuses of mothers nutrient restricted during pregnancy, would have decreased ribosomal protein expression. This could potentially result in compromised function since these cellular subunits play a central role in protein synthesis and cellular energetics. Fetal baboons from mothers fed as ad lib controls (CTR) or globally nutrient restricted (MNR) by 30% from 30 - 165 days of gestation (term ~ 184 days in length) were studied. At necropsy, the average body weight of CTR mothers had increased by 11.3% while that of MNR mothers had decreased by 5.5% from before pregnancy. Body weights of MNR fetuses were 17% smaller than CTR fetal weights, but fetal brains were not different. As measured by gene array, 24 of 75 ribosomal protein mRNAs detected were decreased. Protein expression of 7 of 8 ribosomal proteins, assessed by semi-quantitative immunohistochemistry, was significantly (p< 0.05) or marginally (p > 0.05 < 0.1) decreased. The brains of growth-restricted fetuses are often assumed to be normal because of brain growth sparing. However, the present findings regarding ribosomal protein expression, strongly suggest that nutrient restriction in pregnancy, regardless of cause, inhibits protein synthesis in the fetal brain. In addition, these effects may be exacerbated if continued postnatally with possible effects on important protein dependent processes such as long-term memory storage.