Hepatic Gene Expression Profiling of American Kestrels (Falco sparverius) Exposed In Ovo to Three Alternative Brominated Flame Retardants

Simple Summary Brominated flame retardants are added to many consumer products to reduce flammability. While some of these compounds have been or are being phased out due to toxicity concerns, many other substitute or alternative flame retardant chemicals are still in use and being detected in the environment. There is growing evidence that these alternatives exhibit properties and environmental fates similar to those they replaced. However, little information is available on their potential toxic effects in wildlife. Here, the effects of several flame retardants on American kestrel hatchlings at concentrations observed in wild birds, were investigated by examining gene expression changes in the liver. Effects on the immune, thyroid, and other biological pathways were observed, suggesting that birds exposed as developing embryos in the egg can still exhibit effects upon hatching. A number of brominated flame retardants (BFRs) have been reported to interfere with the thyroid signaling pathway and cause oxidative stress in birds, yet the underlying shifts in gene expression associated with these effects remain poorly understood. In this study, we measured hepatic transcriptional responses of 31 genes in American kestrel (Falco sparverius) hatchlings following in ovo exposure to one of three high-volume alternative BFRs: 1,2-bis(2,4,6-tribromophenoxy) ethane (BTPBE), bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), or 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB). Hatchling kestrels exhibited shifts in the expression of genes related to oxidative stress (CYP, GSTA, SOD, and GPX1), thyroid hormone metabolism and transport (DIO1, DIO2, and TTR), lipid and protein metabolism (PPAR, HMGCR, FAB1, and LPL), and cytokine-mediated inflammation (TLR3, IL18, IRF7, STAT3, RACK1, and CEBPB). Male and female hatchlings differed in which genes were differentially expressed, as well as the direction of the effect (up- vs. downregulation). These results build upon our previous findings of increased oxidative stress and disrupted thyroid signaling pathway in the same hatchlings. Furthermore, our results indicate that inflammatory responses appear to occur in female hatchlings exposed to BTBPE and EHTBB in ovo. Gene expression analysis revealed multiple affected pathways, adding to the growing evidence that sublethal physiological effects are complex and are a concern for birds exposed to BTBPE, EHTBB, or TBPH in ovo.