Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation.

BACKGROUND AND AIMS: Moderately reduced maternal nutrient availability during pregnancy has adverse effects on the fetuses' growth and metabolism during and after pregnancy. The aim of this study was to explore effects of maternal nutrition restriction (MNR) on key metabolites of the fetal energy metabolism, particularly amino acids (AA), nonesterified fatty acids (NEFA), acylcarnitines and phospholipids. These effects may reflect mechanisms relating MNR to later adverse outcomes. METHODS AND RESULTS: Plasma and liver samples of fetal baboons, whose mothers were fed ad libitum (CTR) or MNR (70% of CTR), were collected at 0.5 and 0.9 gestation (G - term 184 days). Metabolites were measured with liquid chromatography coupled to mass spectrometry. In both, CTR and MNR, fetal metabolic profiles changed markedly between 0.5G and 0.9G. Fetal liver glucose concentrations were strongly increased. Hepatic levels of NEFA, sphingomyelins, and alkyl-linked phospholipids increased while plasma NEFA and acyl-linked phospholipids levels decreased with progression of gestation. At 0.5G, MNR fetal plasma levels of short- and medium-chain acylcarnitines were elevated, but did no longer differ between groups at 0.9G. At 0.9G, plasma levels of methionine and threonine as well as hepatic threonine levels were lower in the MNR group. CONCLUSION: Small differences in the concentrations of plasma and liver metabolites between MNR and CTR fetuses reflect good adaptation to MNR. Fetal liver metabolic profiles changed markedly between the two gestation stages, reflecting enhanced liver glucose and lipid levels with advancing gestation. Decreased concentrations of AA suggest an up-regulation of gluconeogenesis in MNR.

Ionizing radiation-induced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus.

The occurrence of radiation-induced apoptosis in normal brain was investigated using an animal model of radiosurgery. Adult male Fischer rats aged 3 to 4 months were subjected to single dose convergent beam irradiation (10 Gy). Apoptotic cell death was determined by in situ labeling of DNA nick ends (TUNEL) and light microscopic evaluation of cell morphology. Five hours after irradiation, a highly significant increase of apoptotic cells in the subgranular zone of the dentate gyrus was paralleled by a corresponding significant decrease of cells immunoreactive for the proliferation marker Ki-67. Morphology, location and distribution of cells affected by radiation-induced apoptosis in the dentate gyrus subgranular zone, together with NeuN-immunohistochemistry, support the contention that these cells belong to the immature progenitor population responsible for neurogenesis in the adult rat hippocampus.