An investigation on different mechanisms of endocrine disruption in fish and molluscs
- Autores: Ángeliki-Kalliopi Lysimachou
- Directores de la Tesis: Ricardo Marcos Dauder (dir. tes.), Cinta Porte Visa (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2009
- Idioma: inglés
- Tribunal Calificador de la Tesis: Daniela Candia Carnevali (presid.), Mercedes Blazquez Peinado (secret.), José M. Ruiz (voc.)
- Materias:
- Enlaces
- Resumen
This thesis investigates the different mechanisms of endocrine dysruption in fish and molluscs following laboratory exposures to three types of compounds: the pharmaceutical and xenoestrogen ethynylestradiol (EE2), the human lipid regulator gemfibrozil (GEM) and the organotins tributyltin (TBT) and triphenyltin (TPT), which are known to induce imposex in female gastropod snails. The first part demonstrates that EE2, which is used in contraceptive pills for its strong estrogenic action, induces neurosteroidogenesis in juvenile Atlantic salmon following 3-days in-vivo exposure to environmental concentrations of the compound. More specifically it induces brain P450aromB mRNA and aromatase activity levels, as well as typical estrogenic responses such as plasma vitellogenin (VTG) and ERalpha mRNA levels. Furthermore, EE2 was found to interfere with the entire hypothalamus-pituitary-interrenal axis by inducing StAR protein, P450scc and CYP11beta gene expression, both in the brain and head-kidney of juvenile Atlantic salmon following 3-days exposure to the compound. 7-days exposure of juvenile Atlantic salmon salmo salar to the organotin TBT, known for its "androgenic" action, inhibited both P450arom isoforms A and B and caused a decrease in aromatase activity but the later was not significant. The fact that ERalpha gene expression and VTG levels showed a tendency to increase instead of decreasing, suggests that the primary action of TBT may not be aromatase inhibition. Exposure of juvenile Eels Anguilla anguilla to the human lipid regulator and rodent peroxisome proliferator GEM for 24 or 96 h resulted in modulation of the hepatic enzymes involved in phase I metabolism following 24 h exposure but this modulation was not present following 96h of exposure. GEM had very little effect on the enzymatic activities of Phase II enzymes. However, it induced the activity of the enzymes involved in peroxisome proliferation (AOX and CAT) following 96h exposure but to a much lesser extent than what it has been observed in rodents indicating that GEM may not act as a peroxisome proliferator in fish. The second part of the thesis shows that imposex susceptible gastropod species have a different adrogen metabolism by examining the metabolism of androstenedione (AD) in three gastropod species: Bolinus brandaris, Hexaplex trunculus and Marisa cornuarietis. Furthermore, in-vitro exposure to TPT and TBT modulated AD metabolism only in females and in a different manner showing that succeptibility to TBT or TPT varies between compounds, species and gender. The last part of the thesis deals with the effects of TPT on the endocrine system of Marisa cornuarietis following 1 week waterborne exposure to environmental concentrations of the compound. More specifically it focuses on the effects of TPT on esterified and free testosterone and estradiol levels, androstenedione metabolism and fatty acid metabolism and lipid homeostasis. Thus TPT was shown to modulate esterified steroids in females but not in males. No alterations were observed in androstenedione metabolism, including the activity of the enzyme aromatase. Furthermore, TPT decreased the percentage of total lipids and fatty acid contents and this decrease was more potent in females. The decrease in FA and lipids is confirmed by the observed induction of AOX in females with is responsible for the oxidation of fatty acids. One-week exposure to TPT caused alterations in the fatty acid profile both in terms of their saturation degree and chain length and these modulations were significant only in females. Thus TPT interferes with the lipid metabolism of Marisa cornuarietis, which could explain the observed changes in steroid fatty acids esters.
