Low copper and brain abnormalities in fetus from triethylene tetramine dihydrochloride-treated pregnant mouse.
The effects of prenatal triethylene tetramine dihydrochloride (Trien-2HCl) exposure on fetal mice have been investigated on gestational day 19. Trien-2HCl was given throughout pregnancy at levels of 0 (control), 3,000, 6,000, or 12,000 ppm as drinking water, ad libitum. At the level of 12,000 ppm, the frequency of total resorption tended to be high and that of fetal viability tended to be low, as compared to controls. Decreased maternal weight was observed in body, but not in liver, at the level of 12,000 ppm. Fetal body and cerebrum weights significantly decreased at the levels of 6,000 and 12,000 ppm; however, fetal liver weight remained unchanged. Maternal serum copper concentration was not affected by the Trien-2HCl. Fetal copper concentrations of liver and cerebrum were significantly lower in the Trien-2HCl-treated groups than in the controls, with levels decreasing in a dose-related manner. When the copper and zinc concentrations in the group treated at 12,000 ppm were compared with those in controls, significant decreases in both metals were observed in placenta but not in maternal liver. Changes in fetal zinc concentration varied by tissues: i.e., an increase in liver and no change in cerebrum. Fetal abnormalities were frequently observed in brain, and the frequency was increased with increasing levels of the Trien-2HCl. These results suggest that fetal brain abnormalities caused by Trien-2HCl may be due in part to induction of copper deficiency, which is almost equivalent to that in brindled mutant mouse.
Tanaka
H
H
Division of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Yamanouchi
M
M
Imai
S
S
Hayashi
Y
Y
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D003300:Copper / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D008809:Mice, Inbred C3H; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014266:Trientine / Q000008:administration & dosage / Q000633:toxicity*; D015032:Zinc / Q000378:metabolism
D003300:Copper; D015032:Zinc; D014266:Trientine