Title : Sex differences in the effects of prenatal bisphenol A exposure on autism-related genes and their relationships with the hippocampus functions
Autism spectrum disorder (ASD) is a neurodevelopmental disorder inexplicably biased towards males. Although prenatal exposure to bisphenol A (BPA) has recently been associated with the ASD risk, whether BPA dysregulates ASD-related gene that known to be involved in neuronal viability, neuritogenesis, and learning/memory in the developing brain remains unclear. In this study, transcriptome profiling by RNA-seq analysis of hippocampus isolated from neonatal pups prenatally exposed to BPA was conducted and revealed a list of differentially expressed genes (DEGs) associated with ASD. Among the DEGs, several ASD candidate genes (e.g. Mief2, Eif3h, Cux1, and Atp8a1) were dysregulated and showed sex differences in response to BPA exposure. Moreover, we found that prenatal BPA exposure increased neurite length, the number of primary neurites, and the number of neurite branches, but reduced the size of the hippocampal cell body in both sexes of the offspring. However, in utero exposure to BPA decreased the neuronal viability and the neuronal density in the hippocampus and impaired learning/memory only in the male offspring while the females were not affected. Interestingly, the expression of several ASD-related genes showed a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory. The findings from this study suggest that prenatal BPA exposure alters the expression of ASD-linked genes in the hippocampus involved in neuronal viability, neuritogenesis, and learning/memory in a sex-dependent manner, and these genes may play an important role in the risk and the higher prevalence of ASD in males subjected to prenatal BPA exposure.
What will audience learn from your presentation?
• This finding demonstrates that prenatal BPA exposure has a negative impact on the ASD-related gene expressions which are known to be involved in neuronal viability, neuritogenesis, and/or learning/memory.
• The correlation analysis between the gene expression levels and neurological functions shows a significant correlation with a male-specific pattern.
• This finding indicated that exposure to BPA at the safety level disrupts the gene expression and neurological function in the hippocampus so the safety level of BPA should be reconsidered