Transplacental effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the temporal modulation of Sp1 DNA binding in the developing cerebral cortex and cerebellum

Gestational exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, (dioxin) often leads to neurodevelopmental and neurobehavioral deficits, which clearly suggest the involvement of the central nervous system. The objective of this study was to determine the effects of an acute, gestational exposure to dioxin on the developmental expression profile of a transcription factor (Sp1) that is involved in growth and differentiation in the developing brain of F, generation pups. Timed-pregnant Harlan Sprague Dawley rats were exposed to single oral doses of 0.25, 0.5, and 1.0 mug dioxin/kg body weight or vehicle corn oil on gestation day 15. Electrophoretic mobility shift assays (EMSA) of the nuclear extracts from the cerebral cortex and cerebellum of the resulting pups, on postnatal days (PND) 3, 5, 10, 15, 20 and 30, with an Sp1 consensus oligonucleotide sequence revealed modulations in the DNA binding activity of Sp1 as a result of the transplacental dioxin exposure. In the cerebral cortex, a dose-dependent premature peak of Spl DNA-binding on PND 3 was observed when compared with the control animals where Sp1 DNA-binding was maximal on PND 10. In the postnatally-developing cerebellum, a dose-dependent premature peak of Spl DNA binding on PND 5 was observed when compared with the control animals where Spl DNA-binding was maximal on PND 15. The mean birth index, body weight gain, and gross brain weight of the pups were not statistically different from the control animals over the 30 day postnatal period studied. The data obtained on the Sp1 developmental expression profiles in the brain indicate that (1) Sp1 DNA-binding is developmentally regulated and expressed very highly in actively developing brain regions, and (2) a potential consequence of the transplacental effect of dioxin to the fetus is in utero neurotoxicity.