Prenatal Stress Produces Sexually Dimorphic and Regionally Specific Changes in Gene Expression in Hippocampus and Frontal Cortex of Developing Rat Offspring

Abstract

Prenatal stress has been known to induce structural changes in the brain and lead to negative psychological well-being. To further understanding of the mechanisms that underlie these effects, whole genome microarray analysis was used to analyze gene expression changes in the developing brain. Epigenetic changes in the hippocampus and frontal cortex of offspring exposed to stress during gestation were investigated. Biological process ontology and pathway analysis was used to increase understanding of the changes produced in response to prenatal stress. The study identified over 700 genes in the frontal cortex and hippocampus that are differentially expressed following prenatal stress. The epigenetic changes demonstrate sex-dependent and region-specific profiles, exhibiting very little overlap between sexes and brain area. Frontal cortex changes were largely related to neurotransmitter function, whereas hippocampal changes were more prominent in females and concentrated around growth factors. These findings have important implications for generalized intervention strategies using a single methodology for all individuals.