Transcriptome responses in polar cod (Boreogadus saida) liver slice culture exposed to benzo[a]pyrene and ethynylestradiol: insights into anti-estrogenic effects. (September 2021)

• Record Type: Journal Article
• Authors: Yadetie, Fekadu; Brun, Nadja R.; Vieweg, Ireen; Nahrgang, Jasmine; Karlsen, Odd André; Goksøyr, Anders
• Is Part Of: Toxicology in vitro. Volume 75(2021)
• Publication Date: 2021-09
• Subjects: Ahr -- ER -- Polar cod -- Liver -- PAH -- Anti-estrogen; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2021.105193
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Polar cod ( Boreogadus saida ) is a key species in the arctic marine ecosystem vulnerable to effects of pollution, particularly from petroleum related activities. To facilitate studying the effects of those pollutants, we adapted a precision-cut liver slice culture protocol for this species. Using this system on board a research vessel, we studied gene expression in liver slice after exposure to the polycyclic aromatic hydrocarbon (PAH) benzo[ a ]pyrene (BaP), ethynylestradiol (EE2), and their mixtures, to map their molecular targets and examine possible anti-estrogenic effects of BaP. The exposure experiments were performed with BaP alone (0.1, 1, and 10 μM) or in combination with low concentrations of EE2 (5 nM) to mimic physiological estradiol levels in early vitellogenic female fish. Transcriptome analysis (RNA-seq) was performed after 72 h exposure in culture to map the genes and cellular pathways affected. The results provide a view of global transcriptome responses to BaP and EE2, which resulted in enrichment of many pathways such as the aryl hydrocarbon (Ahr) and estrogen receptor pathways. In the mixture exposure, BaP resulted in anti-estrogenic effects, shown by attenuation of EE2 activated transcription of many estrogen target genes. The results from this ex vivo experiment suggest that pollutants that activate the Ahr pathway such as the PAH compound BaP can result in anti-estrogenic effects that may lead to endocrine disruption in polar cod. Highlights: A protocol for ex vivo liver slice culture was adapted for use on board research vessels. Transcriptome responses in polar cod liver slice culture exposed to BaP, EE2, and their mixture were mapped. BaP and EE2 exposure resulted in differential expression of several genes and affected many cellular pathways. BaP exposure resulted in attenuation of estrogen induced gene expression (anti-estrogenic effects).