Teratogenic effects of triethylene tetramine dihydrochloride on the mouse brain

The teratogenic effects of triethylene tetramine dihydrochloride (Trien-2HCl) on fetal mouse brain were studied on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 mg/liter as drinking water, ad libitum. Mean litter size and live fetus per dam at birth were not significantly different among the four groups. The frequency of gross brain abnormalities in live fetus at birth such as hemorrhages, delayed ossification in cranium, hydrocephaly, exencephaly, and microcephaly increased with increasing levels of the drug. Microscopically, disorganization of neuronal cell layers, spongiform changes in white matter, and reduced myelin development were noted in the coronally sectioned cerebrum from Trien-2HCl-treated fetus. These abnormal findings increased dose-dependently in regard to the extent and severity at the levels of 6,000 and 12,000 mg/liter. No such changes were observed in the cerebrum of controls. These results suggest that microscopic changes in fetal brain caused by Trien-2HCl may be in part similar to those in brindled mutant mouse. Special attention should be paid to the developing fetal brain when Trien-2HCl is used during pregnancy.