PMID- 16120747 OWN - NLM STAT- MEDLINE DCOM- 20051115 LR - 20161124 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 88 IP - 1 DP - 2005 Nov TI - Toxicogenomic profile of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the murine fetal heart: modulation of cell cycle and extracellular matrix genes. PG - 231-41 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and similar environmental contaminants have been demonstrated to be potent cardiovascular teratogens in developing piscine and avian species. In the present study, we investigated the effects of TCDD on gene expression during murine cardiovascular development. C57Bl6N pregnant mice were dosed with 1.5, 3.0, or 6.0 microg TCDD/kg on gestational day (GD) 14.5, and microarray analysis was used to characterize the global changes in fetal cardiac gene expression on GD 17.5. TCDD significantly altered expression of a number of genes involved in xenobiotic metabolism, cardiac homeostasis, extracellular matrix production/remodeling, and cell cycle regulation. Interestingly, while the AhR-responsive genes Cyp1A1, Cyp1B1, Ugt1a6, and Ahrr, were all induced by TCDD in the fetal murine heart, other AhR-responsive genes, Cyp1a2, Nqo1, and Gsta1, were not. Quantitative real-time polymerase chain reactions confirmed the changes in expression of several G1/S-type cyclins and extracellular matrix-related genes. These results demonstrate the global changes in cardiac gene expression that result from TCDD exposure of the fetal murine heart and implicate genes involved in cell cycle and extracellular matrix regulation in TCDD-induced cardiac teratogenicity and functional deficits. FAU - Thackaberry, E A AU - Thackaberry EA AD - College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. FAU - Jiang, Z AU - Jiang Z FAU - Johnson, C D AU - Johnson CD FAU - Ramos, K S AU - Ramos KS FAU - Walker, M K AU - Walker MK LA - eng GR - ES012335/ES/NIEHS NIH HHS/United States GR - ES012855/ES/NIEHS NIH HHS/United States GR - P30 ES12072/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050824 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Environmental Pollutants) RN - 0 (Polychlorinated Dibenzodioxins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 0 (Teratogens) SB - IM MH - Animals MH - Cell Cycle/*drug effects/genetics MH - Dose-Response Relationship, Drug MH - Environmental Pollutants/*toxicity MH - Extracellular Matrix/*drug effects/genetics MH - Female MH - Fetal Development MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental/*drug effects MH - Heart/*drug effects/embryology MH - Mice MH - Mice, Inbred C57BL MH - Myocardium/metabolism MH - Oligonucleotide Array Sequence Analysis MH - Polychlorinated Dibenzodioxins/*toxicity MH - Pregnancy MH - RNA, Messenger/metabolism MH - Receptors, Aryl Hydrocarbon/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Teratogens/*toxicity EDAT- 2005/08/27 09:00 MHDA- 2005/11/16 09:00 CRDT- 2005/08/27 09:00 PHST- 2005/08/27 09:00 [pubmed] PHST- 2005/11/16 09:00 [medline] PHST- 2005/08/27 09:00 [entrez] AID - kfi301 [pii] AID - 10.1093/toxsci/kfi301 [doi] PST - ppublish SO - Toxicol Sci. 2005 Nov;88(1):231-41. doi: 10.1093/toxsci/kfi301. Epub 2005 Aug 24.