title: 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.affiliation: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D045744:Cell Line, Tumor; D002972:Cleft Palate / Q000139:chemically induced; D003025:Clubfoot / Q000139:chemically induced; D005260:Female; D005333:Fetus; D015870:Gene Expression / Q000187:drug effects; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D008591:Meningomyelocele / Q000139:chemically induced; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000002:abnormalities; D013723:Teratogens / Q000633:toxicity*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D007335:Insulin-Like Growth Factor II