Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats

• Published in: Toxicology letters Vol. 272; pp. 68 - 74
• Main Authors: Hall, Samantha M., Coulter, Sherry J., Knudsen, Gabriel A., Sanders, J. Michael, Birnbaum, Linda S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2017
• Subjects: Administration, Oral; Animals; Female; Flame Retardants - toxicity; Gene expression; Immune System Phenomena - drug effects; Immune System Phenomena - genetics; Immunosuppression; Liver - drug effects; Liver - immunology; Polybrominated Biphenyls - toxicity; Rats; Rats, Wistar; Tetrabromobisphenol A; Transcriptome - drug effects; Uterine toxicity; Uterus - drug effects; Uterus - immunology; Rats; Immunosuppression; Gene expression; Tetrabromobisphenol A; Uterine toxicity
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2017.03.008

•Perturbation of biological pathways in TBBPA-exposed female rats was studied.•Gene expression changes were observed with microarray and validated with ddPCR.•Genes in immune response pathways in uterus were downregulated following TBBPA.•Immunosuppression may play a role in uterine tumor formation after TBBPA exposure. Tetrabromobisphenol A (TBBPA) is a brominated flame retardant used globally at high volumes, primarily in the epoxy resin of circuit boards. It has been detected in the environment and in humans. The National Toxicology Program found that chronic oral TBBPA treatment of 250mg/kg and higher caused an increased incidence of uterine lesions in female Wistar Han rats. The present laboratory has previously reported changes in gene expression associated with estrogen homeostasis in liver and uterine tissue of adult female Wistar Han rats after five days of gavage with 250mg/kg of TBBPA. Microarray analysis of tissue from these same TBBPA-treated rats was performed to detect additional pathways perturbed by TBBPA. Microarray analysis of uterine tissue detected downregulation of genes in pathways of the immune response following TBBPA treatment. These results, along with validation of associated gene expression changes using droplet digital PCR, are reported here. Our findings suggest mechanisms that may be related to estrogen-mediated immunosuppression.