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Changes in the expression of genes involved in the ovarian function of rats caused by daily exposure to 3-methylcholanthrene and their prevention by α-naphthoflavone.
Rhon-Calderón, Eric Alejandro; Toro, Carlos Alejandro; Lomniczi, Alejandro; Galarza, Rocío Alejandra; Faletti, Alicia Graciela.
Afiliação
  • Rhon-Calderón EA; Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, Paraguay 2155, 16º P, (C1121ABG) Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Toro CA; Primate Genetics Section, Division of Neuroscience, Oregon National Primate Research Center, OHSU, Beaverton, OR, 97006, USA.
  • Lomniczi A; Primate Genetics Section, Division of Neuroscience, Oregon National Primate Research Center, OHSU, Beaverton, OR, 97006, USA.
  • Galarza RA; Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, Paraguay 2155, 16º P, (C1121ABG) Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Faletti AG; Universidad de Buenos Aires, Facultad de Medicina, Dto. de Toxicología y Farmacología, Buenos Aires, Argentina.
Arch Toxicol ; 92(2): 907-919, 2018 Feb.
Article em En | MEDLINE | ID: mdl-29094188
Daily exposure to low doses of 3-methylcholanthrene (3MC) during the pubertal period in rats disrupts both follicular growth and ovulation. Thus, to provide new insights into the toxicity mechanism of 3MC in the ovary, here we investigated the effect of daily exposure to 3MC on selected ovarian genes, the role of the aryl hydrocarbon receptor (AhR) and the level of epigenetic remodeling of histone post-transcriptional modifications. Immature rats were daily injected with 3MC (0.1 or 1 mg/kg) and mRNA expression of genes involved in different ovarian processes were evaluated. Of the 29 genes studied, 18 were up-regulated, five were down-regulated and six were not altered. To assess whether AhR was involved in these changes, we used the chromatin immunoprecipitation assay. 3MC increased AhR binding to promoter regions of genes involved in Notch signaling (Hes1, Jag1), activation of primordial follicles (Cdk2), cell adhesion (Icam1), stress and tumor progression (Dnajb6), apoptosis (Bax, Caspase-9) and expression of growth and transcription factors (Igf2, Sp1). Studying the trimethylation and acetylation of histone 3 (H3K4me3 and H3K9Ac, respectively) of these genes, we found that 3MC increased H3K4me3 in Cyp1a1, Jag1, Dnajb6, Igf2, Notch2, Adamts1, Bax and Caspase-9, and H3K9Ac in Cyp1a1, Jag1, Cdk2, Dnajb6, Igf2, Icam1, and Sp1. Co-treatment with α-naphthoflavone (αNF), a specific antagonist of AhR, prevented almost every 3MC-induced changes. Despite the low dose used in these experiments, daily exposure to 3MC induced changes in both gene expression and epigenomic remodeling, which may lead to premature ovarian failure.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzoflavonas / Receptores de Hidrocarboneto Arílico / Folículo Ovariano / Metilcolantreno Limite: Animals Idioma: En Revista: Arch Toxicol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Argentina País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzoflavonas / Receptores de Hidrocarboneto Arílico / Folículo Ovariano / Metilcolantreno Limite: Animals Idioma: En Revista: Arch Toxicol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Argentina País de publicação: Alemanha