Influence of perfluoroalkyl acids and other parameters on circulating thyroid hormones and immune-related microRNA expression in free-ranging nestling peregrine falcons

Abstract Exposure to certain perfluoroalkyl acids (PFAAs) can have considerable effects on the endocrine and immune systems, although such effects remain largely uncharacterized in wildlife. Using an apex avian predator, we investigated possible relationships of thyroid hormones (THs), specifically free (F) and total (T) thyroxine (FT4; TT4) and triiodothyronine (FT3; TT3), and the expression of an immune-related microRNA biomarker (i.e., miR-155), with the concentrations of 11 PFAAs in nestling peregrine falcons (Falco peregrinus). Nestling peregrines (n = 56; usually two chicks of each sex per nest) were blood sampled when 23 ± 4 days old in urban and rural regions of the Laurentian Great Lakes Basin (Ontario, Canada) in 2016 and 2018. The circulating concentrations of several PFAAs were significantly associated with THs and estimated thyroid gland activity (TT3:TT4; FT3:FT4), including PFHxS (FT3; FT3:FT4), PFDS (TT3; TT3:TT4), PFOA (TT4; FT3:FT4), PFTeDA (TT4; FT3:FT4), PFHxDA (TT4; TT3:TT4) and ΣPFCAs (TT4). Our novel evaluation of miR-155 in peregrine nestlings identified significantly negative relationships of plasma miR-155 counts with PFHxS and PFOA concentrations, indicating potential down-regulation of miR-155 expression and impaired immunity. Several PFAA homologues significantly predicted the variation in THs and miR-155 in conjunction with year (e.g., inter-annual differences in weather, ambient temperature, rainfall), region (urban/rural), nestling age, and/or diet (trophic position; δ15N), which suggests that multiple environmental and biological stressors, including PFAA exposure, influenced thyroid activity and immune function in these nestlings. Further research is warranted to identify the mechanisms and additional impacts of PFAA-related thyroid and immune disruption on the growth, development, and health risks in developing birds.