Introduction: Glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) are distributed in the brain, and they are particularly dense in the hippocampus. The two receptors are implicated in stress-related psychiatric diseases, such as anxiety, autism spectrum disorders (ASD) and depression. This study aims to investigate the alterations in neurological behaviour and the expression of GRs and MRs in male offspring from prenatal stress-exposed dams that were subjected to chronic stress.

Methods: In our study, we conducted the elevated plus maze (EPM) test on adult offspring of pregnant mice exposed to chronic stress, as well as on mice in the control group, to examine their neurological behaviors. Expression levels of GRs, MRs, and interleukin 6 (IL-6) were detected by Real- Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT PCR). After euthanizing the adult mice from both groups, we dissected their cortex and hippocampus for immunofluorescence staining.

Results: We observed an increase in the IL-6 mRNA content in the cerebral cortex of male offspring from the stress group, which was accompanied by the activation of microglial cells. Additionally, the relative mRNA expression levels of GRs and MRs in the hippocampus of male offspring from the stress group were found to be decreased. As a result, adult offspring from the stress group exhibited anxiety-like behavior.

Discussion: The observed reduction in hippocampal GR and MR expression, alongside increased cortical IL-6 and anxiety-like behavior in male offspring, suggests that prenatal stress disrupts neuroendocrine and inflammatory pathways, supporting previous findings on stress-induced neurodevelopmental vulnerability, although further studies are needed to address sex differences, long-term behavioral outcomes, and causal mechanisms.

Conclusion: Our study indicates that chronic prenatal stress induces anxiety like behaviour in offspring and decreases the expression levels of GRs and MRs.

Keywords: Prenatal stress, glucocorticoid receptors, mineralocorticoid receptors, neurodevelopment, anxiety-like behavior, inflammation.

link of study: https://www.eurekaselect.com/article/151373

Highlights

• Prenatal Stress and Neurodevelopment: Chronic maternal stress during pregnancy exerts long-term programming effects on the offspring’s brain, particularly affecting regions involved in emotional regulation and stress feedback.

• Receptor Expression Changes: Both glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs)—densely distributed in the hippocampus—were significantly downregulated in adult male offspring exposed to prenatal stress.

• Inflammatory Activation: Prenatal stress induced increased interleukin-6 (IL-6) mRNA expression in the cortex and microglial activation, indicating a sustained neuroinflammatory state.

• Behavioral Outcome: Offspring from stressed dams displayed anxiety-like behaviors in the Elevated Plus Maze (EPM), consistent with disrupted neuroendocrine and immune homeostasis.

• Mechanistic Insight: The findings suggest a dual mechanism—neuroendocrine dysregulation (via reduced GR/MR signaling) and neuroimmune activation (via increased IL-6)—underlying behavioral vulnerability following prenatal stress.

• Translational Implications: These data provide experimental support for the concept of fetal programming, offering insight into how early-life stress exposure increases susceptibility to psychiatric and emotional disorders in adulthood.

Discussion

The reduction in hippocampal GR and MR expression observed in prenatally stressed offspring suggests long-term programming effects on the HPA axis. Decreased receptor expression likely diminishes hippocampal feedback sensitivity to circulating glucocorticoids, resulting in sustained corticosterone release during stress. Such prolonged activation of stress pathways can impair neuronal plasticity, synaptic transmission, and learning processes in the hippocampus—mechanisms previously linked to anxiety and depressive phenotypes.

Conclusion – Key Takeaways

• Chronic prenatal maternal stress leads to adult offspring behavioural changes (anxiety-like behaviour) coupled with neuroendocrine (GR/MR) and inflammatory (IL-6, microglia) alterations.

• The hippocampal GR/MR reductions likely impair stress‐feedback regulation, while cortical inflammation may influence higher‐order emotional processing.

• Future directions include sex comparisons, mechanistic and epigenetic studies, and translation to human behavioural/emotion–voice/body language phenotypes.