Developmental programming: Transcriptional regulation of visceral and subcutaneous adipose by prenatal bisphenol-A in female sheep

Background Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood. Objective To determine the impact of prenatal BPA exposure on the transcriptome of VAT and SAT adipose depots. Methods RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Differences in transcriptional profiling of SAT and VAT in controls and the effect of prenatal BPA treatment on individual genes and gene pathways were determined. Results There were 179 differentially expressed genes (p adjusted 2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways. Conclusion Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.