Prenatal bisphenol A exposure perturbs sex-dependent transcriptomic regionalization of autism-associated genes in the developing brain

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and behavioral regulation. Its etiology arises from a combination of genetic vulnerabilities and environmental influences. Bisphenol A (BPA) is an endocrine-disrupting chemical found in plastic-containing materials, including micro- and nanoplastic pollutants. Recent studies have shown that prenatal BPA exposure can alter behavior and the expression of genes related to autism and neurodevelopment. METHODS: This study integrated and reanalyzed published RNA sequencing datasets from the hippocampus and prefrontal cortex of rat offspring prenatally exposed to BPA through maternal intragastric administration during gestation to investigate the effects of prenatal BPA exposure on transcriptomic regionalization. Quantitative RT-PCR was performed to evaluate selected RNA-seq findings in individual, non-pooled biological samples. The associations between differentially expressed genes (DEGs) and ASD candidate genes were assessed via a hypergeometric distribution analysis. RESULTS: Prenatal BPA exposure was associated with altered transcriptomic profiles in the hippocampus and prefrontal cortex, together with sex-dependent changes in regional expression contrasts between these brain regions. Several ASD-relevant genes, including Msx2, Syncrip, Agtr2, and Myh9, showed altered regional expression patterns following prenatal BPA exposure. Genes showing altered regional expression contrasts after BPA exposure were annotated by IPA with functions, upstream regulators, and canonical pathways relevant to neurodevelopment and neurological disorders. Exploratory correlation analyses further identified region- and sex-dependent associations between disrupted regional gene-expression patterns and behavioral measures. CONCLUSIONS: This reanalysis suggests that prenatal BPA exposure is associated with altered regional transcriptomic patterning in the developing rat brain and identifies candidate genes and pathways for future mechanistic and replication studies.