title: Nonmonotonic response of vitellogenin and estrogen receptor α gene expression after octylphenol exposure of Cichlasoma dimerus (Perciformes, Cichlidae).
abstract: In oviparous vertebrates, vitellogenin (VTG) is mainly produced by the liver in response to estrogen (E2) and its synthesis is traditionally 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 (NP) 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 and estrogen receptors (ERs) gene expression after waterborne exposure to 0.15, 1.5, 15, and 150μg/L OP for up to 1 month (0, 1, 3, 7, 14, 21, and 28 days). At the end of the experiment, histological features of exposed fish included active hepatocytes 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 150μg/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. No VTG and very low levels of ERα were detected in control male livers, but an up-regulation of both genes was found in males exposed to 0.15 or 150μg/L OP. Moreover, VTG transcripts were significant as early as day 3 or day 1 of exposure to these OP concentrations, respectively. Nearly no response was detected in 1.5 and 15μg/L OP exposed-fish. Data was curve-fitted evidencing a nonmonotonic dose-response curve. Interestingly, ERβ2 mRNA expression was augmented above baseline levels only when males were exposed to the lowest OP concentration. We speculate that genomic control of vitellogenesis is under control of multiple steroid receptors with different affinities for ligands. ERβ isoform, only up-regulated with very low concentrations of ligand, would act as a sensors of OP (or E2) to induce ERα and VTG. With high OP concentrations, the expression of ERα isoform is promptly augmented, with the concomitant VTG transactivation.
authors.affiliation: Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Argentina; IBBEA, CONICET-UBA, Argentina. Electronic address: genovese@bg.fcen.uba.ar.
authors.forename: G
authors.initials: G
authors.lastname: Genovese
authors.affiliation: Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Regueira
authors.affiliation: Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Argentina; IBBEA, CONICET-UBA, Argentina.
authors.forename: R H
authors.initials: RH
authors.lastname: Da Cuña
authors.affiliation: Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Argentina.
authors.forename: M F
authors.initials: MF
authors.lastname: Ferreira
authors.affiliation: Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Argentina.
authors.forename: M L
authors.initials: ML
authors.lastname: Varela
authors.affiliation: Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Argentina; IBBEA, CONICET-UBA, Argentina.
authors.forename: F L
authors.initials: FL
authors.lastname: Lo Nostro
mesh_terms: D000818:Animals; D023681:Cichlids / Q000235:genetics* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D010636:Phenols / Q000633:toxicity*; D013737:Testis / Q000187:drug effects; D014819:Vitellogenins / Q000235:genetics* / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D010636:Phenols; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; C474055:octylphenol
keywords: Cichlid fish; Estrogen receptors; Nonmonotonic dose–response; Octylphenol; Vitellogenin gene expression