The Pharmacokinetics of Cadmium in the Dually Perfused Human Placenta

  • Patrick J. Wier
  • Richard K. Miller
Part of the Trophoblast Research book series (TR)


Cadmium is reported to be a significant occupational hazard to over 100,000 workers employed in the mining and processing of this metal (NIOSH publication number 76–192). Because cadmium is released into the environment by mining and numerous manufacturing processes, the general population is exposed to cadmium in air, food, and water (Friberg et al., 1974; Nriagu, 1982). Cigarette smoking is, in addition, an important route of exposure to cadmium (Friberg et al., 1974). The occurrence of exposure to cadmium in the general population has been documented by analyses of the cadmium content in human tissue (Gross et al., 1976). Cadmium is found in human placentae at levels from 0.04 to 1.6 nmole Cd/g (Miller and Shaikh, 1983)


  1. Arizono, K., Ota, S., and Ariyoshi, T. (1981) Purification of metallothionein-like protein in rat placenta. Bull. Environ. Contam. Toxicol. 27, 671–677.PubMedCrossRefGoogle Scholar
  2. Chen, R.W. Wagner, P.A., Hoekstra, W.G., and Ganther, H.E. (1974) Affinity labelling studies with 109-cadmium in cadmium-induced testicular injury in rats. J. Reprod. Fertil. 38, 293–306.Google Scholar
  3. Danielsson, B.R.G. and Dencker, L. (1984) Effects of cadmium on the placental uptake and transport to the fetus of nutrients. Biol. Res. PR 5 (3), 93–101.Google Scholar
  4. di Sant’Agnese, P.A., Jensen, K., Levin, A.A., and Miller, R.K. (1983) Placental toxicity of cadmium: an ultrastructural study. Placenta 4, 149–163.CrossRefGoogle Scholar
  5. Friberg, L., Piscator, M., Nordberg, G., and Kjellstrom, T. (1974) Cadmium in the Environment II. Chemical Rubber Company, Cleveland, Ohio.Google Scholar
  6. Gross, S.B., Yeager, D.W., and Middendorf, M.S. (1976) Cadmium in liver, kidney, and hair of humans, fetal through old age. J. Toxicol. Environ. Hlth. 2, 153–167.CrossRefGoogle Scholar
  7. Hanlon, D.P., Specht, C., and Ferm, V.H. (1982) The chemical status of cadmium ion in the placenta. Environ. Res. 27, 89–94.PubMedCrossRefGoogle Scholar
  8. Kagi, J.H.R., Himmelhock, S.R., Wanger, P.D., Bethone, J.L., and Vallee, B.L. (1974) Equine hepatic and renal metallothioneins. Purification, molecular weight, amino acid composition, and metal content. J. Biol. Chem. 249, 3537–3542.PubMedGoogle Scholar
  9. Lafont, J., Rouanet, J.M., Besancon, P., and Moretti, J. (1976) Existence d’une metallothioneine das le placenta. C.R. Acad. Sci. (Paris) 283, 417–420.Google Scholar
  10. Levin, A.A., Plautz, J.R., di Sant’Agnese, P.A., and Miller, R.K. (1981) Cadmium: placental mechanisms of fetal toxicity. Placenta (Suppl. 3 ), 303–318.Google Scholar
  11. Levin, A.A., Miller, R.K., and di Sant’Agnese, P.A. (1983) Heavy metal alterations of placental function: a mechanism for the induction of fetal toxicity of cadmium. In: Reproductive and Developmental Toxicity of Metals, (eds.), T. Clarkson, G. Nordberg, and P.R. Sager, Plenum Press, New York, pp. 633–654.CrossRefGoogle Scholar
  12. Lowry, O.H., Roseberg, N.J., Farr, A.L., and Randall, R.J. (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  13. Lucis, O.J., Lucks, R., and Shaikh, Z.A. (1972) Cadmium and zinc in pregnancy and lactation. Arch. Environ. Hlth. 25, 14–22.CrossRefGoogle Scholar
  14. Miller, R.K. and Shaikh, Z. (1983) Prenatal metabolism: metals and metallothionein. In: Reproductive and Developmental Toxicity of Metals, (eds.), T. Clarkson, G. Nordberg, and P.R. Sager, Plenum Press, New York, pp. 153–204.Google Scholar
  15. Miller, R.K., Wier, P.J., Maulik, D., and di Sant’Agnese, P.A. (1985) Human placenta in vitro: characterization during 12 h of dual perfusion. In: Contrib. Gynecol. Obstet., (eds.), H. Schneider and J. Dancis, Karger, Basel, pp. 77–84.Google Scholar
  16. Nriagu, J.O. (1982) Cadmium in the Environmental, Parts I and II, John Wiley and Sons, New York.Google Scholar
  17. Onosaka, S. and Cherian, M.G. (1981) The induced synthesis of metallothionein in various tissues of rat in response to metals. I. Effects of repeated injection of cadmium salts. Toxicol. 22, 91–101.CrossRefGoogle Scholar
  18. Samarawickrama, G.P. and Webb, M. (1979) Acute effects of cadmium on the pregnant rat and embryo-fetal development. Environ. Hlth. Persp. 28, 245–249.CrossRefGoogle Scholar
  19. Waalkes, M.P., Poisner, A.M., Wood, G.W., and Klaassen, C.D. (1984) Metallothionein-like proteins in human placenta and fetal membranes. Toxicol. Appl. Pharmacol. 74, 179–184.PubMedCrossRefGoogle Scholar
  20. Webb, M. (1979) The metallothioneins. In: The Chemistry, Biochemistry and Biology of Cadmium, (ed.), M. Webb, Elsevier/North Holland, Biomedical Press, Amsterdam.Google Scholar
  21. Webb, M. (1983) Endogenous metal binding proteins in the control of Zn, Cu, Cd, and Hg metabolism during prenatal and post-natal development. In: Reproductive and Developmental Toxicity of Metals, (eds.), T. Clarkson and G. Nordberg, Plenum Press, New York, pp. 655–674.CrossRefGoogle Scholar
  22. Webb, M. and Samarawickrama, G.P. (1981) Placental transport and embryonic utilization of essential metabolites in the rat at the teratogenic dose of cadmium. J. Appl. Toxicol. 1, 270–277.PubMedCrossRefGoogle Scholar
  23. Wier, P.J., Miller, R.K., Maulik, D., and di Sant’Agnese, P.A. (1983) Bidirectional transfer of alpha-aminoisobutyric acid by the perfused human placental lobule. TrophoblastRes. 1, 37–54.Google Scholar
  24. Wier, P.J., Miller, R.K., Maulik, D., and di Sant’Agnese, P.A. (1986) Viability of the human placental lobule during 12 hours of dual perfusion, Submitted.Google Scholar
  25. Wolkowski, R.M. (1974) Differential cadmium-induced embryotoxicity in two inbred mouse strains: analysis of inheritance of the response to cadmium and of the presence of cadmium in fetal and placental tissues. Teratol. 10, 243–262.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Patrick J. Wier
    • 1
  • Richard K. Miller
    • 1
  1. 1.Department of Obstetrics and Gynecology, Pharmacology, and Radiation Biology and Biophysics, Division of ToxicologyUniversity of Rochester School of Medicine and DentistryRochesterUSA

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