Choline deficiency alters angiogenesis in the fetal brain

Abstract

Maternal dietary choline intake during pregnancy alters normal fetal neurogenesis and associates with lifelong changes in memory function in the offspring. Mitosis is decreased, while apoptosis is increased, in neural progenitor cells of the hippocampus in the fetuses of rodent dams fed choline deficient (CD) diets. We now report that maternal choline deficiency increases angiogenesis in the fetal hippocampus. Timed pregnant C57BL/6 mice were fed a CD or control (CT) AIN‐76 diet from day 12 to day 17 (E17) of gestation. Fetal brains were studied at day E17. We found increased numbers of endothelial cell‐clusters expressing factor VIII in the fetal hippocampal area in the CD group (68±3 in CD vs. 54±3 in CT, p <0.01). In other experiments, neural progenitor cells from E14 fetal mouse brains were grown in low choline (5 μM) or control (70 μM) for 72 h. In the low choline group we observed increased relative gene expression for vascular endothelial factor (VEGF) (5.03±2.24 in CD vs. 0.52± 0.19 in CT, p<0.001) and angiopoietin 2 (ANGPT2) (4.92±1.7 in CD vs. 1.43±0.6 in CT, p<0.05). We conclude that the changes in neurogenesis are the trigger for altered angiogenesis, probably by increasing VEGF and ANGPT2 signaling. This phenomenon contributes to the effects that maternal intake of choline has on fetal brain development. This research is supported by the grant from NIH‐ AG09525.