title: Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats.
abstract: 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.
authors.affiliation: Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, United States.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Hall
authors.affiliation: Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, United States.
authors.forename: Sherry J
authors.initials: SJ
authors.lastname: Coulter
authors.affiliation: Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, United States. Electronic address: gabriel.knudsen@nih.gov.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Knudsen
authors.affiliation: Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, United States.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sanders
authors.affiliation: Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, United States.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D055633:Immune System Phenomena / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000276:immunology; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D017208:Rats, Wistar; D059467:Transcriptome / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000276:immunology
chemical_list: D005411:Flame Retardants; D011075:Polybrominated Biphenyls; C020806:tetrabromobisphenol A
keywords: Gene expression; Immunosuppression; Rats; Tetrabromobisphenol A; Uterine toxicity