Delayed response in the rat frontal lobe transcriptome to perinatal exposure to the flame retardant BDE-47

BDE-47 is the most prevalent congener of polybrominated diphenyl ethers, which are widely used flame retardants, and is known for endocrine and behavioral disrupting properties in animals. Transient effect on spontaneous motor activity in rats following perinatal exposure to BDE-47 at low doses, relevant to human exposure, was reported in our previous study. The objective of this study was to screen for the long-term effects on gene expression in the brain of rats perinatally exposed to BDE-47. Wistar dams were exposed to BDE-47 (0.002 and 0.2 mg kg(-1) body weight) from gestation day 15 to postnatal day (PND) 20. Total RNA was extracted from the whole brain at PND10 and the brain frontal lobes at PND41 and hybridized to whole-genome RNA expression microarrays. The genes, differentially expressed 1.5-fold, were analyzed with the DAVID bioinformatics resources for cluster and gene-term enrichment. At PND41, clusters of genes involved in nerve impulse transmission, nervous system development and functioning, and core biosynthetic process were altered, including several downregulated genes of cation channels. Representation of LINE1 RNA was decreased significantly. Altered expression of genes involved in neurodevelopment occured at least 3 weeks after the last exposure and the behavioral manifestation of low dose BDE-47 toxicity.