Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency

The function of metallothionein in zinc homeostasis was examined by using m ice homozygous for knockout (KO) of the metallothionein-I or -II (MT-I and MT-II) genes. Pregnant MT-I/II KO mice or control mice were fed a zinc-defi cient (1 mu g/g or 5 mu g/g) diet or a zinc-adequate (50 mu g/g) diet durin g specific periods of pregnancy, and the effects on morphogenesis of the em bryos were determined at day 14 of pregnancy (day 1 = vaginal plug). In the homozygous MT-I/II KO, as well as in the nontransgenic control mice, sever e dietary zinc deficiency (1 mu g/g) beginning on day 1 of pregnancy was em bryotoxic acid teratogenic, and the majority of the embryos in both strains were dead by mid-gestation. However, 53% of the surviving embryos in the M T-I/II KO mice were morphologically abnormal compared to only 32% of the em bryos in the control mice. In subsequent experiments, moderate dietary zinc deficiency (5 mu g/g beginning on day 1 of pregnancy or 1 mu g/g dietary z inc beginning on day 8 of pregnancy) exerted teratogenic, but not embryotox ic effects. Embryos in the MT-I/II KO mice were 260 to 290% as likely to de velop abnormally than were embryos in the control mice fed these same diets . These results demonstrate that the expression of the MT-I and -II genes i n pregnant females improves reproductive success during maternal dietary zi nc deficiency.