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

Show simple item record Lee, Jamie Prokopec, Stephenie D. Watson, John D. Sun, Ren X. Pohjanvirta, Raimo Boutros, Paul C. 2016-05-30T13:15:02Z 2016-05-30T13:15:02Z 2015-08-20
dc.identifier.citation 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 .
dc.identifier.other PURE: 53602651
dc.identifier.other PURE UUID: 65985b0b-89d3-4ace-b7ef-0e62328b2910
dc.identifier.other WOS: 000359764000003
dc.identifier.other Scopus: 84939491217
dc.description.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. en
dc.format.extent 14
dc.language.iso eng
dc.relation.ispartof BMC Genomics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 2,3,7,8-tetrachlorodibenzo-p-dioxin
dc.subject TCDD
dc.subject Aryl hydrocarbon receptor
dc.subject AHR
dc.subject Sex differences
dc.subject AH RECEPTOR
dc.subject C57BL/6 MICE
dc.subject MOUSE-LIVER
dc.subject 413 Veterinary science
dc.title Male and female mice show significant differences in hepatic transcriptomic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin en
dc.type Article
dc.contributor.organization Departments of Faculty of Veterinary Medicine
dc.contributor.organization Food Hygiene and Environmental Health
dc.contributor.organization Raimo Pohjanvirta / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1471-2164
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
art_3A10.1186_2Fs12864_015_1840_6.pdf 3.136Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record