Maternal Ethanol Exposure Is Associated With Decreased Plasma Zinc and Increased Fetal Abnormalities in Normal but Not Metallothionein-Null Mice
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 24, Issue 2, pages 213–219, February 2000
How to Cite
Carey, L. C., Coyle, P., Philcox, J. C. and Rofe, A. M. (2000), Maternal Ethanol Exposure Is Associated With Decreased Plasma Zinc and Increased Fetal Abnormalities in Normal but Not Metallothionein-Null Mice. Alcoholism: Clinical and Experimental Research, 24: 213–219. doi: 10.1111/j.1530-0277.2000.tb04593.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication July 6, 1999; accepted November 26, 1999.
Ethanol profoundly affects fetal development, and this is proposed to be due primarily to a transient fetal zinc (Zn) deficiency that arises from the binding of Zn by metallothionein (MT) in the maternal liver. Zn homeostasis and fetal outcome were investigated in normal (MT+/+) and metallothionein-null (MT-/-) mice in response to ethanol exposure.
Mice were treated with saline or ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) on day 8 of gestation (Gd8), and the degree of fetal dysmorphology was assessed on Gd18. The incidence of external abnormalities was significantly increased in offspring from MT+/+ dams exposed to ethanol, where 27.4% of fetuses were affected. MT-/- ethanol-, MT+/+ saline-, and MT-/- saline-treated dams had fetuses in which the frequencies of abnormalities were 2.2, 6.4, and 6.9%, respectively. To investigate Zn homeostasis, nonpregnant mice were killed at intervals over 16 hr after ethanol injection. Liver MT concentrations in MT+/+ mice were increased 20-fold by 16 hr, with a significant elevation evident by 4 hr, whereas liver Zn levels were also significantly increased by 2 hr and maintained for 16 hr. In parallel with these changes, plasma Zn concentrations in MT+/+ mice decreased by 65%, with minimum levels of 4.5±0.3 μmol/liter at 8 hr. Conversely, MT-/- mice exhibited increased plasma Zn concentrations, with peak values of 20.8±0.3 observed at 4 hr.
These findings link the teratogenic effect of ethanol to the induction of maternal MT and the limitation of fetal Zn supply from the plasma.