Cadmium-induced gene expression changes in the mouse embryo, and the influence of pretreatment with zinc.
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.
Kultima
Kim
K
Department of Pharmaceutical Biosciences, Division of Toxicology, Uppsala University, BMC, Uppsala, Sweden.
Fernández
Estíbaliz L
EL
Scholz
Birger
B
Gustafson
Anne-Lee
AL
Dencker
Lennart
L
Stigson
Michael
M
D000818:Animals; D001499:Bayes Theorem; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005865:Gestational Age; D007274:Injections, Intraperitoneal; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D017967:Zinc Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride; D019256:Cadmium Chloride