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

Tim Dalton, Kai Fu, George C. Enders, Richard D. Palmiter, Glen K. Andrews

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis 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 μmol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 μmol 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 μmol 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.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalEnvironmental Health Perspectives
Volume104
Issue number1
DOIs
StatePublished - Jan 1 1996

Fingerprint

metallothionein
Metallothionein
toxicology
Cadmium
Toxicology
Transgenic Mice
cadmium
Histology
Testis
histology
pregnancy
Injections
Fertility
fertility
Pregnancy
Spermatogenesis
Pregnancy Rate
analysis
effect
Necrosis

Keywords

  • Cadmium
  • Metallothionein
  • Peri-implantation
  • Reproductive
  • Testes
  • Toxicology
  • Transgenic mice

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium. / Dalton, Tim; Fu, Kai; Enders, George C.; Palmiter, Richard D.; Andrews, Glen K.

In: Environmental Health Perspectives, Vol. 104, No. 1, 01.01.1996, p. 68-76.

Research output: Contribution to journalArticle

Dalton, Tim ; Fu, Kai ; Enders, George C. ; Palmiter, Richard D. ; Andrews, Glen K. / Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium. In: Environmental Health Perspectives. 1996 ; Vol. 104, No. 1. pp. 68-76.
@article{955ba22d0b3240c98a2bec4e853797ee,
title = "Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium",
abstract = "Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis 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 μmol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 μmol 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 μmol 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.",
keywords = "Cadmium, Metallothionein, Peri-implantation, Reproductive, Testes, Toxicology, Transgenic mice",
author = "Tim Dalton and Kai Fu and Enders, {George C.} and Palmiter, {Richard D.} and Andrews, {Glen K.}",
year = "1996",
month = "1",
day = "1",
doi = "10.1289/ehp.9610468",
language = "English (US)",
volume = "104",
pages = "68--76",
journal = "Environmental Health Perspectives",
issn = "0091-6765",
publisher = "Public Health Services, US Dept of Health and Human Services",
number = "1",

}

TY - JOUR

T1 - Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium

AU - Dalton, Tim

AU - Fu, Kai

AU - Enders, George C.

AU - Palmiter, Richard D.

AU - Andrews, Glen K.

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis 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 μmol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 μmol 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 μmol 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.

AB - Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis 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 μmol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 μmol 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 μmol 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.

KW - Cadmium

KW - Metallothionein

KW - Peri-implantation

KW - Reproductive

KW - Testes

KW - Toxicology

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=0030041435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030041435&partnerID=8YFLogxK

U2 - 10.1289/ehp.9610468

DO - 10.1289/ehp.9610468

M3 - Article

C2 - 8834864

AN - SCOPUS:0030041435

VL - 104

SP - 68

EP - 76

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 1

ER -