Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium

Journal Article · Mon Jan 01 04:00:00 EST 1996 · Environmental Health Perspectives

DOI:https://doi.org/10.1289/ehp.9610468· OSTI ID:391060

Dalton, T; Fu, Kai; Andrews, G K ^[1]; Enders, G C; Palmiter, R D ^[2]

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1. Univ. of Kansas Medical Center, Kansas City, KS (United States)
2. Univ. of Washington, Seattle, WA (United States)

Exposure to low levels of cadmium reduces fertility. In male mice spermatogensis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 {mu}mol Cd/Kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 {mu}mol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 {mu}mol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility. 65 refs., 6 figs., 1 tab.

• Sponsoring Organization: USDOE
• OSTI ID: 391060
• Journal Information: Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: 1 Vol. 104; ISSN 0091-6765; ISSN EVHPAZ
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BIOLOGICAL EFFECTS
CADMIUM
FERTILITY
METALLOTHIONEIN
MICE
RESPONSE MODIFYING FACTORS
TRANSGENIC MICE