Increased hepatic Igf2 gene expression involves C/EBPβ in TCDD-induced teratogenesis in rats.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant for reproductive toxicity that was suggested to be linked to growth factors. Insulin-like growth factor 2 (Igf2) has great effects on the control of fetal growth. We hypothesize it might participate in the TCDD-induced toxic events. The expression of Igf2 in TCDD-induced fetal rat and rat hepatoma BRL-3A cells was monitored by real-time quantitative RT-PCR and Western blotting. Electrophoresis mobility shift assay and chromatin immunoprecipitation were performed to identify the CCAAT/enhancer binding protein β (C/EBPβ) responsive element in the Igf2 P3-promoter. The transcriptional activity of the Igf2 P3-promoter was detected by luciferase assay. Pregnant rats exposed to TCDD showed a modest incidence of fetal death, fetal growth restriction and fetal malformation. The levels of Igf2 mRNA and IGF2 protein were elevated in TCDD-exposed fetal liver. Temporal expression of Igf2 was also induced by TCDD in BRL-3A cells. A C/EBPβ responsive element was identified at position -743 to -732 of the Igf2 P3-promoter, and its binding was enhanced by TCDD exposure through upregulation of the C/EBPβ protein. The transcriptional activity of the Igf2 P3-promoter was also augmented by TCDD. Our results showed that TCDD may induce Igf2 gene expression through the transactivation of C/EBPβ, which may be linked to the developmental effects of TCDD in rats.

• Authors: Jun Wang, Xiaoliang Liu, Tingting Li, Caixia Liu, Yanyan Zhao
• Journal: Reproductive toxicology (Elmsford, N.Y.) (Reprod Toxicol) Vol. 32 Issue 3 Pg. 313-21 (Nov 2011) ISSN: 1873-1708 [Electronic] United States
• PMID: 21777668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• CCAAT-Enhancer-Binding Protein-beta
• Polychlorinated Dibenzodioxins
• Teratogens
• Insulin-Like Growth Factor II

Topics

• Abnormalities, Drug-Induced
• Animals
• CCAAT-Enhancer-Binding Protein-beta (metabolism)
• Cell Line, Tumor
• Cleft Palate (chemically induced)
• Clubfoot (chemically induced)
• Female
• Fetus
• Gene Expression (drug effects)
• Insulin-Like Growth Factor II (genetics, metabolism)
• Liver (drug effects, metabolism)
• Male
• Maternal Exposure
• Meningomyelocele (chemically induced)
• Polychlorinated Dibenzodioxins (toxicity)
• Pregnancy
• Rats
• Rats, Wistar
• Tail (abnormalities)
• Teratogens (toxicity)