Prenatal stress diminishes gender differences in behavior and in expression of hippocampal synaptic genes and proteins in rats.

The study determined whether there were gender differences in the expression of hippocampal genes in adult rats in association with dissimilarity in their behavior, and how these were affected by prenatal stress. Pregnant Wistar rats were subjected to varied stress once daily on days 14-20 of gestation. Adult female offspring of control rats showed significantly less anxiogenic behavior in the elevated plus maze and better discrimination between a novel and familiar object than males in the object recognition test. These gender differences in behavior were markedly attenuated by prenatal stress. Using Affymetrix DNA chip technology on hippocampal extracts prepared from littermates of the offspring used for behavioral tests, we found that 1,680 genes were differentially expressed in control males and females. The gender difference in gene expression was decreased to 11% (191 genes) by prenatal stress. In both sexes, processes like the translational machinery, mitochondrial activity, and cation transport were downregulated compared to controls, but there was a greater suppression of genes involved in vesicle trafficking, regulation of synaptic plasticity, and neurogenesis in females than in males. This was compensated by a higher expression of other components of vesicle trafficking, microtubule-based processes, and neurite development. Prenatal stress decreased the expression of 19 Rab proteins in females and five Rabs in males, but a compensatory increase of Rab partner proteins and effectors only occurred in females. Exposure to stress decreased the expression of synaptic proteins, synaptophysin, and synaptopodin in prenatally stressed males and females and increased those of PSD-95 and NR1 subunit of the N-methyl-D-aspartic acid (NMDA) glutamate receptor only in females. The study provides an unbiased view of key genes and proteins that act as gender dependent molecular sensors. The disruption of their expression by adverse early life stress may explain the alterations that occur in behavior.