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Hepatic transcriptomic alterations for bis(2-ethylhexyl) tetrabromophthalate (TBPH) after 5-day exposure in rats

ABSTRACT: To identify liver transcripts differentially expressed due to treatment with bis(2-ethylhexyl) tetrabromophthalate (TBPH), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.07, 0.71, 7.06, 70.6 or 706 mg/kg TBPH, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array. A total of 0,0,0,0, and 0 gene transcripts were differentially expressed due to TBPH treatment after exposure to 0.07, 0.71, 7.06, 70.6 or 706 mg/kg TBPH (false discovery rate (FDR) < 0.05).

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE153365 | GEO | 2020/07/15

REPOSITORIES: GEO

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Project description:17alpha-ethinylestradiol (EE2) is one of the most potent estrogens that have the ability to interfere with the endocrine system of fish. The objective was to investigate the effects and mechanisms of action caused by 60 days of dietary exposure to 0.2 mg EE2/kg and 0.07 mg EE2/kg feed in female largemouth bass (LMB) during the reproductive season. Microarrays and pathway analyses were performed on hepatic tissues to identify genes and biological processes altered in female LMB by EE2 exposure. The hypothesis was that the two concentrations of EE2 would produce dose-response changes in sensitive genes. Body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. The 0.2 mg EE2/kg feed exposure reduced the gonadosomatic index (GSI) by 75%, and plasma levels of E2 and T were reduced by over 90%. Plasma VTG was increased by approximately 100% (from 4 to 8mg/ml) by the 0.2 mg/kg treatment. T levels, from the 0.07 mg EE2/kg feed, reduced GSI by approximately 30% and circulating E2 and T by ~80% but did not affect VTG concentrations. We found 1,594 and 1,165 genes were significantly affected (p<0.05) by the 0.07 mg EE2/kg feed and 0.2 mg EE2/kg feed, respectively. Gene ontology (GO) analysis revealed that there were different biological processes regulated by the two concentrations of EE2. Pathway analysis showed that the 0.07 mg EE2/kg feed exposure caused differential regulation of genes associated with fatty acid biosynthesis and glycolysis, indicating some metabolic effects. In contrast, the 0.2 mg EE2/kg feed exposure altered transcription of genes involved in immune response and apoptosis, suggesting a toxic response at this concentration. These results suggest that the two concentrations demonstrated distinct physiological responses, with the higher concentration inducing complete endocrine disruption in LMB. These findings demonstrate the usefulness of microarrays to identify possible biomarkers and modes of toxic action to dietary exposure in LMB. Two concentrations of EE2 would produce dose-response changes in sensitive genes. Female LMB were fed 5 days per week for 60 days with floating pellets that contained 0.07 or 0.2 mg/kg of EE2.

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Hepatic transcriptomic alterations for bis(2-ethylhexyl) tetrabromophthalate (TBPH) after 5-day exposure in rats

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