Cadmium-induced forelimb ectrodactyly: a proposed mechanism of teratogenesis.
We have attempted to elucidate the mechanism of cadmium teratogenesis utilizing inbred mouse strains sensitive (C57BL/6J) or resistant (SWV) to the embryotoxic effect of this common heavy metal contaminant. Carbonic anhydrase activity of whole-embryo homogenates was moderately depressed in C57BL/6J mice compared to a slight and transient decrease in the resistant SWV mice. Embryonic erythrocytes were similarly examined, and the cadmium did not have any effect on carbonic anhydrase activity in either strain. Likewise, histochemical examination of carbonic anhydrase activity did not reveal any effect of cadmium in the embryos of their strain. Generally, the zinc concentration of embryos was not affected by cadmium administration. However, increased levels of zinc were observed in cadmium-exposed yolk sacs of both strains suggesting that cadmium produces an adverse effect on yolk sac function. Untreated C57BL/6J units (embryo plus surrounding extraembryonic membranes), embryos, and yolk sacs had much lower hemoglobin concentrations than those observed in untreated SWV units, embryos, and yolk sacs. Additionally, cadmium exposure significantly decreased C57BL/6J embryonic hemoglobin levels on gestation day 10 (PM) and increased C57BL/6J yolk sac hemoglobin levels on gestation days 10 (AM) and 10 (PM). No difference in hemoglobin concentration was observed between untreated and cadmium-treated SWV embryos or yolk sacs. We propose that cadmium induces forelimb ectrodactyly by creating an acidotic embryonic environment and that the primary site at which cadmium exerts its teratogenic effect might be the yolk sac.
D000014:Abnormalities, Drug-Induced / Q000196:embryology* / Q000201:enzymology; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002257:Carbonic Anhydrase Inhibitors / Q000633:toxicity; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000201:enzymology; D005552:Forelimb / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology; D005865:Gestational Age; D006454:Hemoglobins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D015017:Yolk Sac / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D002257:Carbonic Anhydrase Inhibitors; D006454:Hemoglobins; D002104:Cadmium; D002256:Carbonic Anhydrases; D015032:Zinc