Sexual differences in long-term effects of prenatal chronic mild stress on anxiety-like behavior and stress-induced regional glutamate receptor expression in rat offspring

•PCMS increased anxiety-like behavior in both male and female offspring.•EPM induced sex-specific changes in GluR expression in different brain regions.•PCMS induced robust changes of GluR expression when subjected to anxiogenic test.•PCMS is a potential risk factor for developing anxiety in offspring.

Severe adverse life events during pregnancy may increase the risk of anxiety disorders in the offspring. Glutamate receptors are neurobiological targets in anxiety disorders. In this study, we investigated the effects of prenatal chronic mild stress (PCMS) on anxiety-like behavior by using elevated plus maze (EPM), and evaluated the effects of PCMS and/or anxiogenic challenge on glutamate receptors in different brain regions. Our results showed that PCMS increased anxiety-like behavior in both male and female offspring. Moreover, compared with the male naïve rats, male EPM rats showed a significant reduction of mGluR2/3 in the prefrontal cortex, mGluR1 and mGluR2/3 in the hippocampus, and increments of mGluR5, NR1, NR2B and PSD95 in the amygdala. In contrast, compared with female naïve rats, female EPM rats showed decreased levels of mGluR5 in the hippocampus, and mGluR2/3 and mGluR5 in the prefrontal cortex, and increased levels of NR2B and PSD95 in the amygdala. Furthermore, PCMS seemed not to affect the baseline expression of glutamate receptors in adult offspring, but induced significant alterations of them triggered by anxiogenic challenge with a sex difference. These data strengthen the pathophysiological hypothesis that prenatal stress as a risk factor involves in the development of anxiety disorder in the offspring.