Liver‐specific decrease in Tff3 gene expression in infant mice perinatally exposed to 2, 3, 7, 8‐tetrabromodibenzofuran or 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin. Issue 2 (12th July 2021)

• Record Type: Journal Article
• Authors: Kimura, Eiki; Suzuki, Go; Uramaru, Naoto; Kakeyama, Masaki; Maekawa, Fumihiko
• Is Part Of: Journal of applied toxicology. Volume 42:Issue 2(2022)
• Page Start: 305
• Page End: 317
• Publication Date: 2021-07-12
• Subjects: 2, 3, 7, 8‐tetrabromodibenzofuran -- 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin -- developmental toxicity -- liver -- toxic equivalency factor -- trefoil factor 3; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4220
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Polybrominated dibenzo‐ p ‐dioxins and dibenzofurans (PBDD/DFs) are byproducts of brominated flame retardants and can cause adverse health effects. Although exposure to polychlorinated (PC) DD/DFs induces toxic effects, including liver injury and neurobehavioral disorder, little is known about toxicities associated with PBDD/DF exposure. Thus, we examined effects of perinatal exposure to brominated congener on the infant mouse. Gene expression in several organs, such as the liver and brain, was analyzed in mouse offspring born to dams administered 2, 3, 7, 8‐tetrabromodibenzofuran (TBDF; 9 or 45 μg/kg body weight) or 2, 3, 7, 8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD; 3 μg/kg body weight) on gestational day 12.5. An increase in liver size was observed in TBDF‐ or TCDD‐exposed offspring in infancy. Gene microarray analysis revealed that 163 and 36 genes were markedly upregulated and downregulated, respectively, in the liver of TBDF‐exposed mice compared with those in vehicle‐treated mice on postnatal day (PND) 5. Significant increases in Cyp1a1, Cyp1a2, Fmo3, and Pnliprp1 and decreases in Tff3, Ocstamp, Kcnk16, and Lgals2 mRNA levels in TBDF‐exposed offspring on PNDs 5 and 12 were confirmed by quantitative PCR. In particular, a significant reduction in Tff3 mRNA in the liver, but not in the brain, small intestine, colon, and kidney, was observed in offspring perinatally exposed to TBDF or TCDD. Ultrasonic calls of TBDF‐ or TCDD‐exposed offspring on PNDs 3–5 were impaired. Taken together, perinatal exposure to polyhalogenated dioxin/furan congeners disrupts gene expression patterns in the liver and ultrasonic calling during infancy. These results suggest that liver injury may contribute to neurobehavioral disorder. Abstract : Information regarding the toxicity of polybrominated dibenzofurans is currently limited. We revealed that perinatal exposure to 2, 3, 7, 8‐tetrabromodibenzofuran (TBDF) disrupted gene expression patterns in the infant mouse liver and induced a liver‐specific decrease in Tff3 mRNA expression. A reduction in liver Tff3 mRNA expression was also observed in infant mice exposed to 2, 3, 7, 8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD). Ultrasonic calls were impaired by TBDF or TCDD exposure. Collectively, perinatal exposure to polyhalogenated dioxin/furan congeners induces liver injury and neurobehavioral disorder during developmental period.