Thyroid disruption and oxidative stress in American kestrels following embryonic exposure to the alternative flame retardants, EHTBB and TBPH

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

“…The American kestrel ( Falco sparverius ) is an apex predator and an important toxicological model for predatory birds [ 21 ] with relatively high sensitivity to environmental contaminants. We previously reported disruption of thyroid function and increased oxidative stress in American kestrel hatchlings exposed in ovo to environmentally relevant concentrations of BTBPE, EHTBB, and TBPH [ 22 , 23 ]. Specifically, kestrel hatchlings exposed to EHTBB or TBPH in ovo (range: nominal concentrations 10–100 ng/g egg mass) exhibited lower thyroidal colloid (EHTBB and TBPH), as well as higher plasma triiodothyronine (T3) and lower glandular thyroxine (T4) (EHTBB only) [ 23 ].…”

“…We previously reported disruption of thyroid function and increased oxidative stress in American kestrel hatchlings exposed in ovo to environmentally relevant concentrations of BTBPE, EHTBB, and TBPH [ 22 , 23 ]. Specifically, kestrel hatchlings exposed to EHTBB or TBPH in ovo (range: nominal concentrations 10–100 ng/g egg mass) exhibited lower thyroidal colloid (EHTBB and TBPH), as well as higher plasma triiodothyronine (T3) and lower glandular thyroxine (T4) (EHTBB only) [ 23 ]. Additionally, kestrel hatchlings exposed to BTBPE, EHTBB, or TBPH in ovo exhibited altered activity of hepatic deiodinases, enzymes that convert T4 to the biologically active form T3, but the effects of these alternative BFRs on deiodinase activity varied by sex [ 22 , 23 ].…”

“…Specifically, kestrel hatchlings exposed to EHTBB or TBPH in ovo (range: nominal concentrations 10–100 ng/g egg mass) exhibited lower thyroidal colloid (EHTBB and TBPH), as well as higher plasma triiodothyronine (T3) and lower glandular thyroxine (T4) (EHTBB only) [ 23 ]. Additionally, kestrel hatchlings exposed to BTBPE, EHTBB, or TBPH in ovo exhibited altered activity of hepatic deiodinases, enzymes that convert T4 to the biologically active form T3, but the effects of these alternative BFRs on deiodinase activity varied by sex [ 22 , 23 ]. In addition to dysregulation of thyroid signaling, in ovo exposure to BTBPE, EHTBB, and TBPH increases oxidative stress in hatchlings.…”

“…In addition to dysregulation of thyroid signaling, in ovo exposure to BTBPE, EHTBB, and TBPH increases oxidative stress in hatchlings. Kestrel hatchlings exposed to EHTBB and TBPH in ovo exhibited higher glutathione levels [ 23 ]. While these results indicate that in ovo exposure to BTBPE, EHTBB, and TBPH increases oxidative stress and interferes with several components of the thyroid signaling pathway in kestrel hatchlings, the transcriptional responses to in ovo exposure to these alternative BFRs are unknown.…”

“…“Omics” approaches (e.g., transcriptomics, toxicogenomics, and metabolomics) provide insights into pathway perturbations and can identify potential (eco)toxicological mechanisms of action by measuring differentially expressed genes in response to environmental chemicals [ 24 ]. In the present study, we measured hepatic transcript abundance of 31 genes in the same American kestrel hatchlings exposed to EHTBB, TBPH, or BTBPE in ovo, in which we previously reported increased oxidative stress and thyroid system dysregulation using nongenomic biomarkers [ 22 , 23 ]. Given this previous evidence, we hypothesized that in ovo exposure to BTBPE, EHTBB, and TBPH would affect the mRNA expression of detoxification enzymes and genes related to thyroid signaling, and that these changes would be sex-specific.…”