High fat diet-induced maternal obesity alters fetal hippocampal development.

The importance of maternal nutrition for fetal brain development is increasingly recognized. Previous studies have suggested that maternal obesity or maternal exposure to obesogenic diets may permanently alter brain structure and function in the offspring. To test whether maternal exposure to a high-fat diet, prior and during gestation, alters fetal hippocampal development, we fed 8-week old C57BL/6 females with a high-fat diet (60% calories from fat) for 10 weeks prior to matting and 17 days after. Fetal brains at embryonic day E17 were used to determine developmental changes in the hippocampus. We report that maternal exposure to the high-fat diet induced small for gestational age (SGA) status and fetal resorption. The proliferation of neural progenitors was increased in the neuroepithelium from hippocampus and cortex in fetuses from mothers fed the high-fat diet when compared to controls, but decreased within the dentate gyrus (DG). Apoptosis in the hippocampus was decreased (Ammon's Horn and fimbria). The differentiation of calretinin-positive neurons within the DG was also decreased. These data indicate that, under the influence of a maternal high-fat diet administered prior and during gestation, fetal hippocampal development is altered at embryonic day 17, as indicated by region-specific changes in proliferation of neural precursors, decreased apoptosis, and by decreased neuronal differentiation within the dentate gyrus.