Sexual dimorphism of autism-like phenotypes in microglial eIF4E overexpression mice
Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and interaction, and restricted interests or repetitive behaviors. ASD is approximately four times more prevalent in males than in females. In this study, we investigated whether sex hormones or sex chromosomes underlie the male bias in ASD susceptibility.…
Autism spectrum disorder (ASD) is markedly more prevalent in males than females. A mouse model called MG4E was created to study the role of sex hormones and sex chromosomes in this male bias. The MG4E mice exhibit ASD-like characteristics, specifically in social interaction and dendritic spine density. To further investigate, four-core-genotype (FCG) mice, carrying Sry gene manipulations, were crossed with MG4E mice to generate eight different genotypes.
Behavioral tests were conducted to assess social interaction and repetitive behaviors. Dendritic spine density was measured in Thy1-GFP mice. The expression levels of estrogen receptors (ERs) and androgen receptors (AR) were also examined in microglia from both control and MG4E mice.
The results showed that sex hormones, specifically estrogen receptors, were the main cause of the male-biased deficits in social interaction and increased dendritic spine density. At 14 days postnatal, ERs were not detected in microglia, but they were found in neurons. This suggests that sex hormones might indirectly influence microglia-neuron interactions during neurodevelopment by acting on hormone-responsive neurons.
Therefore, the male predisposition to ASD-like traits in MG4E mice is primarily driven by sex hormones, rather than genes located on sex chromosomes.
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