Differential Expression of Endogenous Retroviruses and Inflammatory Mediators in Female and Male Offspring in a Mouse Model of Maternal Immune Activation

Maternal infections during pregnancy and the consequent maternal immune activation (MIA) are the major risk factors for autism spectrum disorder (ASD). Epidemiological evidence is corroborated by the preclinical models in which MIA leads to ASD-like behavioral abnormalities and altered neuroinflammatory profiles, with an increase in pro-inflammatory cytokines and microglial markers. In addition to neuroinflammatory response, an abnormal expression of endogenous retroviruses (ERVs) has been identified in neurodevelopmental disorders and have been found to correlate with disease severity. Our aim was to evaluate the transcriptional profile of several ERV families, ERV-related genes, and inflammatory mediators (by RT real-time PCR) in mouse offspring of both sexes, prenatally exposed to polyinosinic:polycytidylic acid (Poly I:C), a synthetic double-stranded RNA molecule targeting TLR-3 that mimics viral maternal infection during pregnancy. We found that prenatal exposure to Poly I:C deregulated the expression of some ERVs and ERV-related genes both in the prefrontal cortex (PFC) and hippocampus, while no changes were detected in the blood. Interestingly, sex-related differences in the expression levels of some ERVs, ERV-related genes, and inflammatory mediators that were higher in females than in males emerged only in PFC. Our findings support the tissue specificity of ERV and ERV-related transcriptional profiles in MIA mice.

Automated summary

Maternal infections during pregnancy and the consequent maternal immune activation (MIA) are major risk factors for autism spectrum disorder (ASD). Preclinical models have shown that MIA can lead to ASD-like behavioral abnormalities and altered neuroinflammatory profiles. Abnormal expression of endogenous retroviruses (ERVs) has also been identified in neurodevelopmental disorders and is correlated with disease severity. This study aimed to evaluate the transcriptional profile of ERVs and inflammatory mediators in mouse offspring prenatally exposed to Poly I:C, a synthetic double-stranded RNA molecule that mimics viral maternal infection. The findings support the tissue specificity of ERV and ERV-related transcriptional profiles in MIA mice.