Nonmonotonic response of vitellogenin and estrogen receptor alpha gene expression after octylphenol exposure of Cichlasoma dimerus (Perciformes, Cichlidae).

GENOVESE, G.; REGUEIRA, M.; DA CUÑA, R.; FERREIRA, M.F.; VARELA, M.L.; LO NOSTRO, F.

AQUATIC TOXICOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 156 p. 30 - 40

0166-445X

In oviparous vertebrates, vitellogenin (VTG) is mainly produced by the liver in response to estrogen (E2) and its synthesis is tightly coupled to estrogen receptor alpha induction. Even though VTG is a female-specific protein, chemicals that mimic natural estrogens known as xenoestrogens can activate its expression in males, causing endocrine disruption to wildlife and humans. Alkylphenols such as nonylphenol and octylphenol (OP) are industrial additives used in the manufacture of a wide variety of plastics and detergents, and can disrupt endocrine functions in exposed animals. For more than a decade, the freshwater cichlid fish Cichlasoma dimerus has been used for ecotoxicological studies in our laboratory. We recently found an up-regulation of VTG gene expression in livers of male fish exposed to OP, from a silent state to values similar to those of E2-induced fish. To better understand the underlying mechanisms behind the action of xenoestrogens, the aim of this study was to analyze the dose-response relationship of C. dimerus VTG gene expression after waterborne exposure to OP for 0, 1, 3, 7, 14, 21, and 28 days. At the end of the experiment, histological features of exposed fish included active hepatocyes with basophilic cytoplasm and high eosinophilic content in their vascular system due to augmented expression of VTG. In testis, high preponderance of sperm was found in fish exposed to 150 µg/L OP. A classic dose-response down-regulation of the expression of Na+/K+-ATPase, a ?non-gender specific gene? used for comparison, was found with increasing OP concentrations. On the contrary, a time dependent up-regulation of liver VTG gene expression was only found in males exposed to 0.15 or 150 µg/L OP, as early as day 3 or 1 of exposure, respectively; nearly no response was detected in 1.5 and 15 µg/L OP exposed-fish. The results at the end of the experiment were plotted evidencing a nonmonotonic dose-response curve. This kind of response is typical of multiple steroid receptor systems where nonselectivity or receptor down-regulation can occur at high doses of xenoestrogens, as well as up-regulation at low doses. We conclude that extrapolation of results obtained with high doses of xenoestrogens assuming a monotonic dose-response curve can lead to false estimates of safety levels.