Cadmium-induced gene expression changes in the mouse embryo, and the influence of pretreatment with zinc

Reprod Toxicol. 2006 Nov;22(4):636-46. doi: 10.1016/j.reprotox.2006.05.007. Epub 2006 Jun 3.

Abstract

Cadmium (Cd) administered to female C57BL/6 mice on gestation day 8 induces a high incidence of anterior neural tube defects (exencephaly). This adverse effect can be attenuated by maternal pretreatment with zinc (Zn). In this study we used replicated microarray analysis and real-time PCR to investigate gene expression changes induced in the embryo 5 and 10h after maternal Cd exposure in the absence or presence of Zn pretreatment. We report nine genes with a transcriptional response induced by Cd, none of which was influenced by Zn pretreatment, and two genes induced only by combined maternal Cd exposure and Zn pretreatment. We discuss the results in relation to the possibility that Cd is largely excluded from the embryo, that the teratogenic effects of Cd may be secondary to toxicity in extraembryonic tissues, and that the primary protective role of Zn may not be to reverse Cd-induced transcription in the embryo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • Cadmium Chloride / administration & dosage
  • Cadmium Chloride / toxicity*
  • Chlorides / administration & dosage
  • Chlorides / pharmacology*
  • Drug Interactions
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Profiling
  • Gestational Age
  • Injections, Intraperitoneal
  • Male
  • Maternal Exposure / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis / methods
  • Pregnancy
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Time Factors
  • Up-Regulation / drug effects*
  • Up-Regulation / genetics
  • Zinc Compounds / administration & dosage
  • Zinc Compounds / pharmacology*

Substances

  • Chlorides
  • Zinc Compounds
  • zinc chloride
  • Cadmium Chloride