Amelioration of TCDD-induced teratogenesis in aryl hydrocarbon receptor (AhR)-null mice

• DOI: 10.1093/toxsci/47.1.86
• Publication Date: 2002-07-26T22:33:32Z
• Authors: J. M. Peters; M. G. Narotsky; G. Elizondo; P. M. Fernandez-S...; F. J. Gonzalez; B. D. Abbott
• Keywords: Developmental toxicity

The aryl hydrocarbon receptor (AhR) mediates many of the biological effects 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and transcriptional activation genes encoding a number xenobiotic metabolizing enzymes. Prenatal exposure mice to TCDD causes severe alterations in embryo fetal development, including hydronephrosis cleft palate. However, mechanisms underlying these are unclear. In this work, teratogenicity AhR-null was evaluated determine if effect is mediated by AhR. Homozygous wild-type (+/+) or (-/-) female were mated with males same genotype overnight. On gestation day (GD)-10, intubated orally either corn oil (vehicle control) 25 micrograms/kg TCDD. Fetuses examined on GD18 for visceral skeletal alterations. For non-TCDD-exposed litters, all developmental endpoints comparable between genotypes, exception lower incidence large interfrontal bones mice. TCDD-exposed fetuses had significantly greater palate, hydronephrosis, small kidneys, tortuous ureters dilation renal pelves compared fetuses. Interestingly, an increased resorption rate observed exposed Results from work demonstrate that development per se generally unaffected absence AhR other may have compensated loss More importantly, data indicate TCDD-induced teratogenicity. Further, since higher percentage resorptions litters TCDD-treated dams, it possible AhR-independent contribute toxicity.