Male and female mice show significant differences in hepatic transcriptomic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin

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Lee , J , Prokopec , S D , Watson , J D , Sun , R X , Pohjanvirta , R & Boutros , P C 2015 , ' Male and female mice show significant differences in hepatic transcriptomic response to 2,3,7,8-tetrachlorodibenzo- p -dioxin ' , BMC Genomics , vol. 16 , 625 . https://doi.org/10.1186/s12864-015-1840-6

Title: Male and female mice show significant differences in hepatic transcriptomic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin
Author: Lee, Jamie; Prokopec, Stephenie D.; Watson, John D.; Sun, Ren X.; Pohjanvirta, Raimo; Boutros, Paul C.
Contributor: University of Helsinki, Departments of Faculty of Veterinary Medicine
Date: 2015-08-20
Language: eng
Number of pages: 14
Belongs to series: BMC Genomics
ISSN: 1471-2164
URI: http://hdl.handle.net/10138/163034
Abstract: Background: 2,3,7,8-tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 mu g/kg) in adult male and female C57BL/6Kuo mice. Results: Several key findings were revealed by our study. 1) Hepatic transcriptomes varied significantly between the sexes at all doses examined. 2) The liver transcriptome of males was more dysregulated by TCDD than that of females. 3) The alteration of " AHR-core" genes was consistent in magnitude, regardless of sex. 4) A subset of genes demonstrated sex-dependent TCDD-induced transcriptional changes, including Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In addition, a meta-analysis was performed to contrast transcriptomic profiles of various organisms and tissues following exposure to equitoxic doses of TCDD. Minimal overlap was observed in the differences between TCDD-sensitive or TCDD-resistant models. Conclusions: Sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes. In addition, complex interactions between the aryl hydrocarbon and sex hormone receptors may affect the observable differences in sensitivity phenotypes between the sexes. Further work is necessary to better understand the roles of those genes altered by TCDD in a sex-dependent manner, and their association with changes to sex hormones and receptors.
Subject: 2,3,7,8-tetrachlorodibenzo-p-dioxin
TCDD
Aryl hydrocarbon receptor
AHR
Sex differences
ARYL-HYDROCARBON RECEPTOR
FLAVIN-CONTAINING MONOOXYGENASE
ABNORMAL LIVER DEVELOPMENT
SPRAGUE-DAWLEY RATS
GENE-EXPRESSION
NUCLEAR TRANSLOCATOR
AH RECEPTOR
C57BL/6 MICE
MOUSE-LIVER
413 Veterinary science
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