| dc.description.abstract | Human activities contribute a significant amount of contaminants to the natural environment. Polycyclic aromatic hydrocarbons (PAHs) and per- and polyfluoroalkyl substances (PFASs) are example of contaminants that threaten the aquatic and wildlife ecosystems, whose occurrence has been reported along the Norwegian coastline. These contaminants bioaccumulate and interfere with biological systems and induce toxicity in organisms. Reproductive development is continuous process throughout an individual´s lifetime and is sensitive to alteration by the presence of contaminants in the environment. The present thesis has employed field, whole animals (in vivo), and cultured tissue (ex vivo) exposure strategies to investigate molecular and cellular toxicological effects of contaminants at environmentally relevant concentrations on the reproductive physiology of female Atlantic cod (Gadus morhua).
In the field study, farmed juvenile cod were caged at Kollevåg bay (capped waste disposal site). After six weeks of caging, fish showed significantly high bioaccumulation of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dichlorodiphenyltrichloroethane (DDT) and hydroxylated PAH metabolites in different tissues. Among biological responses, biomarkers associated with oxidative stress, biotransformation, lipid metabolism and reproduction were significantly affected in cod. In addition to the expression of steroidogenic pathway enzyme genes, we investigated change of transcriptome and lipid profile in the ovary. Transcriptome sequencing showed many differentially expressed genes (DEGs) in cod ovary at Kollevåg stations. These genes were mapped to the pathways that belong to important biological processes such as oxidative stress, DNA damage, cytoskeleton remodelling, apoptosis, epithelial-to-mesenchymal transition (EMT), epigenetic alteration, translation, immunomodulation and lipid metabolism. Besides transcriptional changes, levels of a selected number of lipid classes were also altered in the ovary.
Besides the direct involvement of gonadal cellular pathways, signalling from the dopaminergic neurons is also involved in regulating the hypothalamic-pituitary-gonadal-liver (HPGL) axis. Cod was exposed to PAHs and PFASs at two different doses, low and high, either individually or in combinations. Exposure to the mixture of PAH and PFAS at a high concentration, significantly increased plasma sex steroid (17β-estradiol: E2) levels. We also observed high brain dopamine turnover, as levels of 3,4-Dihydroxyphenylacetic acid (DOPAC) and expression of dopamine active transporter (dat) gene increased in the brain. The participation of dopaminergic machinery in the HPGL-axis was independent of estrogenic biomarkers in the brain.
Ex vivo exposure of cod ovarian slices with long-chain PFASs (PFOS, PFOA and PFNA), given individually and also in combination (mixture) showed that both high exposure concentration of the mixture and PFOS produced a large number of differentially expressed genes (DEGs). Both high PFAS mixture and high PFOS individual exposure shared a large number of DEGs, and pathways that belong to important biological processes such as lipid metabolism, cell adhesion, immunological responses, cellular signalling, cancer and reproduction. In general, our data showed that PFOS is, most probably, the active component in the PFAS mixture that significantly altered the expression of genes and pathways.
Overall, the findings in my thesis can show that excess contaminant levels above environmental quality standards (EQSs) produce alterations and interference with biological machinery and integrity relevant to reproductive development, endocrinology and ovarian physiology. This assumption is based on the findings from the Bay of Kollevåg and further validated with in vivo and ex vivo experiments, suggesting that effective concentrations of these contaminants modulated reproductive endocrinology and physiology, with overt consequences for survival, general health and recruitment. | en_US |
