title: Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals.
abstract: Endocrine disrupting chemicals (EDCs) have the potential to interfere with the hormonal system and may negatively influence human health. Microarray analysis was used in this study to investigate differential gene expression in human peripheral blood cells (PBMCs) after in vitro exposure to EDCs. PBMCs, isolated from blood samples of four male and four female healthy individuals, were exposed in vitro for 18h to either a dioxin-like polychlorinated biphenyl (PCB126, 1μM), a non-dioxin-like polychlorinated biphenyl (PCB153, 10μM), a brominated flame retardant (BDE47, 10μM), a perfluorinated alkyl acid (PFOA, 10μM) or bisphenol (BPA, 10μM). ANOVA analysis revealed a significant change in the expression of 862 genes as a result of EDC exposure. The gender of the donors did not affect gene expression. Hierarchical cluster analysis created three groups and clustered: (1) PCB126-exposed samples, (2) PCB153 and BDE47, (3) PFOA and BPA. The number of differentially expressed genes varied per compound and ranged from 60 to 192 when using fold change and multiplicity corrected p-value as filtering criteria. Exposure to PCB126 induced the AhR signaling pathway. BDE47 and PCB153 are known to disrupt thyroid metabolism and exposure influenced the expression of the nuclear receptors PPARγ and ESR2, respectively. BPA and PFOA did not induce significant changes in the expression of known nuclear receptors. Overall, each compound produced a unique gene expression signature affecting pathways and GO processes linked to metabolism and inflammation. Twenty-nine genes were significantly altered in expression under all experimental conditions. Six of these genes (HSD11B2, MMP11, ADIPOQ, CEL, DUSP9 and TUB) could be associated with obesity and metabolic syndrome. In conclusion, microarray analysis identified that PBMCs altered their gene expression response in vitro when challenged with EDCs. Our screening approach has identified a number of gene candidates that warrant further study.
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Mol, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Wens
authors.forename: P
authors.initials: P
authors.lastname: De Boever
authors.forename: M
authors.initials: M
authors.lastname: Verbeke
authors.forename: K
authors.initials: K
authors.lastname: Hollanders
authors.forename: G
authors.initials: G
authors.lastname: Schoeters
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002478:Cells, Cultured; D016000:Cluster Analysis; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D009765:Obesity / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D052244:Endocrine Disruptors; D018336:Receptors, Aryl Hydrocarbon