Blood Transcriptomics Analysis of Fish Exposed to Perfluoro Alkyls Substances: Assessment of a Non-Lethal Sampling Technique for Advancing Aquatic Toxicology Research

Abstract

In contrast to mammals, the blood from other vertebrates such as fish contains nucleated red cells. Using a fathead minnow (Pimephales promelas) oligonucleotide microarray, we compared altered transcripts in the liver and whole blood after exposure to environmentally relevant concentrations of perfluorooctanesulfonic acid (PFOS) and a mixture of seven types of perfluoro alkyl substances (PFAS), including perfluorooctanoic acid (PFOA). We used quantitative polymerase chain reactions and cell-based assays to confirm the main effects and found that blood responded with a greater number of altered genes than the liver. The exposure to PFAS altered similar genes with central roles in a cellular pathway in both tissues, including estrogen receptor α and peroxisome proliferator activator β and γ, indicating that the genes previously associated with PFAS exposure are differentially expressed in blood and liver. The altered transcripts are involved with cholesterol metabolism and mitochondrial function. Our data confirmed that PFAS are weak xenoestrogens and exert effects on DNA integrity. Gene expression profiling from blood samples not related with the immune system, including very-low-density lipoprotein, vitellogenin, estrogen receptor, and thyroid hormone receptor, demonstrated that blood is a useful tissue for assessing endocrine disruption in non-mammalian vertebrates. We conclude that the use of blood for non-lethal sampling in genomics studies is informative and particularly useful for assessing the effects of pollution in endangered species. Further, using blood will reduce animal use and widen the experimental design options for studying the effects of contaminant exposure on wildlife.

Thyroid Disrupting Effects of Old and New Generation PFAS

“…This increase expression was hypothesized to be involved in a non-correct thyroid hormones binding and consequent alteration of the hypothalamus-pituitary-thyroid axis function. This study highlighted that also small concentrations of organic contaminants may be detected in the bloodstream ( 47 ).…”

“…On the contrary, the recent study by Kim et al., showed an up-regulation of corticotropin releasing hormone b (CRHB), thyrotropin receptor (TSHR), and thyroid transcription factor-1 (NKX2.1) genes which was suggestive of a negative feedback in response to decreased circulating thyroid hormones ( 46 ). Finally, Rodriguez-Jorquera et al., performed a blood transcriptomic analysis in fish exposed to PFAS reporting an up-regulation, mainly promoted by PFOS, of thyroid hormone receptor beta (TR-β) ( 47 ). This increase expression was hypothesized to be involved in a non-correct thyroid hormones binding and consequent alteration of the hypothalamus-pituitary-thyroid axis function.…”

Perfluoroalkyl Substances in Plasma of Smallmouth Bass from the Chesapeake Bay Watershed

“…The relationship between PFAS concentrations in blood/plasma and liver or muscle in smallmouth bass is currently unknown. Plasma/blood provides a potential non-lethal sample, may provide better insights into fish health effects and can be sampled repeatedly from the same individual [36]. It also provides a comparison to human exposure/toxicity as most human studies utilize blood/plasma/serum.…”

Patterns in Serum Toxicokinetics in Peromyscus Exposed to Per‐ and Polyfluoroalkyl Substances

“…In addition, understanding the connection between serum concentrations and dose allows for improved site‐specific ecological risk‐assessment sampling possibilities. For instance, nonlethal sampling methods can aid nuanced effect detection (Rodriguez‐Jorquera et al 2019) as well as refined field sampling and/or monitoring data (Huang et al 2016). With our data, in particular the serum to dose ratio, one could plausibly connect environmental media concentrations with nonlethal samples collected from field‐observed small mammals.…”