Skip to main content
Log in

Zinc deficiency and the developing embryo

  • Review
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The effect ofin utero zinc deficiency on fetal development in rats is reviewed. Attention is paid to the primary biochemical lesion associated with zinc-related teratogenesis and special consideration is given to the central nervous system. Evidence is presented that the thymidine kinase salvage pathway, used for the synthesis of thymidine monophosphate in DNA synthesis, is depressed more in fetal brain tissue than in the liver. In addition, greater reliance appears to be placed on this pathway than onde novo synthesis in the fetal brain than in other tissues. Some consideration is given to the use of in vitro embryo culture in studies relating to neurogenesis, but evidence is presented of a greater capacity of explanted rat embryos to obtain zinc from maternal serum than occurs in vivo.

The rapid onset of a teratogenic zinc deficiency following dietary zinc restriction is again highlighted and further studies are described which demonstrate the critical impact of a single feeding cycle, of 4 d duration, on maternal plasma zinc levels and on the extent and nature of the observed fetal abnormalities. Evidence is presented that by shifting the timing of the high dietary intake/low plasma zinc peak to coincide with a particular 48 h period between days 6 and 10 of pregnancy, the pattern of malformations thus obtained reflected the coincidence of the high dietary intake of zinc-deficient diet and the critical time of morphogenesis of several organ systems.

Whereas diminished plasma zinc levels at term in zinc-deficient animals are generally well correlated with reduced growth and dysmorphogenesis of the offspring, the same is not always found in human studies. In some cases, elevated plasma zinc levels at parturition are found in mothers with growth-retarded children, or vice versa. Experimental studies with rats are reported that suggest that maternal zinc status at term may be higher in dams bearing pups stunted by exposure to a transient zinc deficiency early in pregnancy, which in turn may have reduced the demand for maternal zinc in the later stages of gestation.

The protective effect of zinc on cadmium-induced teratogenesis is discussed, particularly in relation to findings concerning an interaction of these metals in the embryonic yolk sac and thus on preplacental embryonic nutrition. Possible interactions between alcohol and zinc deficiency are also considered and data are presented pointing to increased fetotoxicity and teratogenesis in the presence of both treatments and to a more specific interaction with respect to reduced cell numbers in the developing rat hippocampus. Malondialdehyde levels, which reflect the extent of lipid peroxidation in tissue, are reported to be substantially higher in microsomes from fetal rat livers whenin utero deficiency and gestational alcoholism are combined. The suggestion is made that alcohol and zinc deficiency act independently in the body, but overlap to some extent at the common biochemical locus of membrane lipid peroxidation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. L. S. Hurley and H. Swenerton,Proc. Soc. Exp. Biol. Med. 123, 692 (1966).

    PubMed  CAS  Google Scholar 

  2. S. Jameson,Acta Med. Scand. Suppl. 593, 5 (1976).

    PubMed  CAS  Google Scholar 

  3. K. E. Bergmann, E. Makosch and K. H. Tews,Am. J. Clin. Nutr. 33, 2145 (1980).

    PubMed  CAS  Google Scholar 

  4. C. Stewart, B. Katchan, P. J. Collipp S. Clejan, S. Pudalov and S. Y. Chen,Pediat. Res. 15, 515 (1981).

    Article  Google Scholar 

  5. H. H. Sandstead,Am. J. Clin. Nutr. 26, 1251 (1973).

    PubMed  CAS  Google Scholar 

  6. P. R. Gordon, C. W. Woodruff, H. L. Anderson and B. L. O'Dell,Am. J. Clin. Nutr. 35, 113 (1982).

    PubMed  CAS  Google Scholar 

  7. C. F. Mills, J. Quarterman, J. K. Chesters, R. B. Williams and A. C. Dalgarno,Am. J. Clin. Nutr. 22, 1240 (1969).

    PubMed  CAS  Google Scholar 

  8. I. E. Dreosti, P. C. Grey and P. J. Wilkins,S. Afr. Med. J. 46, 1585 (1972).

    PubMed  CAS  Google Scholar 

  9. J. Warkany and H. G. Petering,Teratology 5, 319 (1972).

    Article  PubMed  CAS  Google Scholar 

  10. L. S. Hurley, J. Gowan and H. Swenerton,Teratology 4, 199 (1971).

    Article  CAS  Google Scholar 

  11. L. S. Hurley and R. E. Shrader, inNeurobiology of the Trace Metals Zinc and Copper, C. C. Pfeiffer, ed., Academic Press, New York, 1972, p. 7.

    Google Scholar 

  12. J. F. Chlebowski and J. E. Coleman, inMetal Ions in Biological Systems, H. Sigel, ed. Dekker, New York, 1971, p. 1.

    Google Scholar 

  13. M. Chvapil,Mid. Clin. N. Am. 60, 799 (1976).

    CAS  Google Scholar 

  14. W. J. Bettger and B. L. O'Dell,Life Sci. 28, 1425 (1981).

    Article  PubMed  CAS  Google Scholar 

  15. A. S. Prasad,Ann. Rev. Toxicol. 20, 393 (1979).

    Article  Google Scholar 

  16. L. S. Hurley,Med. Clin. N. Am. 60, 771 (1976)

    PubMed  CAS  Google Scholar 

  17. L. S. Hurley,Physiol. Rev. 61, 249 (1981).

    PubMed  CAS  Google Scholar 

  18. A. S. Prasad and C. Oberleas,J. Lab. Clin. Med. 83, 634 (1974).

    PubMed  CAS  Google Scholar 

  19. I. E. Dreosti and L. S. Hurley,Proc. Soc. Exp. Biol. Med. 150, 161 (1975).

    PubMed  CAS  Google Scholar 

  20. J. R. Duncan and L. S. Hurley,Proc. Soc. Exp. Biol. Med. 159, 39 (1978).

    PubMed  CAS  Google Scholar 

  21. B. L. O'Dell, inClinical Application of Zinc Metabolism, W. J. Pories, W. H. Strain, J. M. Hsu, and R. L. Woosley, eds., Charles C. Thomas, Springfield USA, 1974, p. 5.

    Google Scholar 

  22. B. L. Vallee and K. H. Falchuk,Phil. Trans. R. Soc. Lond,294, 185 (1981).

    Article  CAS  Google Scholar 

  23. A. Adeloye and J. Warkany,Child's Brain 2, 325 (1976).

    Article  PubMed  CAS  Google Scholar 

  24. C. D. Eckert and L. S. Hurley,J. Nutr. 107, 855 (1977).

    Google Scholar 

  25. I. R. Record and I. E. Dreosti,Nutr. Rep. Int. 20, 749 (1979).

    CAS  Google Scholar 

  26. I. R. Record, I. E. Dreosti and R. M. Smith,Proc. Aust. Biochem. Soc. 13, 98 (1980).

    Google Scholar 

  27. I. E. Dreosti, InNeurobiology of Zinc, Vol. 1, C. J. Frederickson, G. A. Howell and E. J. Kasarskis, eds., Liss, New York, 1984, p. 1.

    Google Scholar 

  28. I. R. Record, I. E. Dreosti, and R. S. Tulsi,J. Exp. Biol. Med. Sci., in press.

  29. L. S. Hurley and R. E. Shrader,Nature 254, 427 (1975).

    Article  PubMed  CAS  Google Scholar 

  30. I. R. Record, I. E. Dreosti, S. J. Manuel, R. A. Buckley, and R. S. Tulsi, inTrace Element Metabolism in Man and Animals, TEMA 5, C. F. Mills, ed., in press.

  31. J. K. Chesters and M. Will,Br. J. Nutr. 30, 555 (1973).

    Article  PubMed  CAS  Google Scholar 

  32. A. J. McMichael, I. E. Dreosti, G. T. Gibson, J. M. Hartshorne, R. A. Buckley, and D. P. Colley,Early Human Development 7 59 (1982).

    Article  PubMed  CAS  Google Scholar 

  33. D. G. Masters, C. L. Keen, B. Lonnerdal, and L. S. Hurley,J. Nutr. 113, 905 (1983).

    PubMed  CAS  Google Scholar 

  34. P. R. Flanagan,J. Nutr. 114, 493 (1984).

    PubMed  CAS  Google Scholar 

  35. L. S. Sever and I. EmanuelTeratology 7, 117 (1973).

    Article  PubMed  CAS  Google Scholar 

  36. A. O. Cavdar, A. Arcasoy, T. Baycu, and O. Himmetoglu,Teratology 22, 141 (1980).

    Article  PubMed  CAS  Google Scholar 

  37. M. H. Solton and D. M. Jenkins,Br. J. Obstet. Gynaecol. 89, 56 (1982).

    Google Scholar 

  38. N. Meadows, W. Ruse, P. W. N. Keeling, J. W. Scopes, and R. P. H. Thompson,Arch. Dis. Child. 58, 807 (1983).

    Article  PubMed  CAS  Google Scholar 

  39. J. Metcoff,Early Human Development 4, 99 (1980).

    Article  PubMed  CAS  Google Scholar 

  40. F. F. Cherry, E. A. Bennett, E. S. Bazzano, L. K. Johnson, G. J. Fosmire, and H. K. Batson,Am. J. Clin. Nutr. 34, 2367 (1981).

    PubMed  CAS  Google Scholar 

  41. J. Doszpod, I. Czeh, and I. Gati,A. Geburtsh. U. Perinat. 187, 273 (1983).

    CAS  Google Scholar 

  42. I. E. Dreosti, A. J. McMichael, G. T. Gibson, R. A. Buckley, J. M. Hartshorne, and D. P. Colley,Nutr. Res. 2, 591 (1982).

    Article  CAS  Google Scholar 

  43. M. W. Breskin, B. S. Worthington-Roberts, R. H. Knopp, Z. Brown, B. Plovie, K. Moffet, and J. L. Mills,Am. J. Clin. Nutr. 38 943 (1983).

    PubMed  CAS  Google Scholar 

  44. J. Parizek,J. Reprod. Fertil. 7, 263 (1964).

    Article  PubMed  CAS  Google Scholar 

  45. L. J. Pierro, inNeurobiology of the Trace Elements, I. E. Dreosti and R. M. Smith, eds., Humana Press, Clifton NJ, 1983, p. 79.

    Chapter  Google Scholar 

  46. R. A. Ahokas, P. V. Dilts, and E. B. LeHaye,Am. J. Obstet. Gynecol. 136 216 (1980).

    PubMed  CAS  Google Scholar 

  47. M. Barr,Teratology 7, 237 (1973).

    Article  CAS  Google Scholar 

  48. V. H. Ferm and S. J. Carpenter,Lab. Invest. 18, 429 (1968).

    PubMed  CAS  Google Scholar 

  49. S. R. Rohrer, S.M. Snow, G. S Born, and R. J. Vetter,Bull. Environ. Contam. Toxicol. 19, 556 (1978).

    Article  PubMed  CAS  Google Scholar 

  50. R. A. Ahokas and P. V. Dilts,Am. J. Obstet, Gynecol. 135, 219 (1979).

    CAS  Google Scholar 

  51. V. A. Ferm, D. P. Hanlon, and J. Urbon,J. Embryol. Exp. Morphol. 22, 107 (1969).

    PubMed  CAS  Google Scholar 

  52. I. R. Record, I. E. Dreosti, S. J. Manuel, and R. A. Buckley,Life Sci. 31, 2735 (1982).

    Article  PubMed  CAS  Google Scholar 

  53. I. R. Record, I. E. Dreosti, and S. J. Manuel,J. Nutr. 112, 1994 (1982).

    PubMed  CAS  Google Scholar 

  54. I. E. Dreosti and I. R. Record,Proc. Nutr. Soc. N. Z. in press.

  55. K. S. Hirsch and L. S. Hurley,Teratology 17, 303 (1978).

    Article  PubMed  CAS  Google Scholar 

  56. R. M. Hackman and L. S. Hurley,Teratology 28, 355 (1983).

    Article  PubMed  CAS  Google Scholar 

  57. A. J. Jackson and H. J. Schumacher,Teratology 19, 341 (1979).

    Article  PubMed  CAS  Google Scholar 

  58. I. E. Dreosti inMechanisms of Alcohol Damage in Utero, Ciba Symposium 105, Pittman, London, 1984, p. 103.

    Google Scholar 

  59. J. F. Sullivan and H. G. Lankford,Am. J. Clin. Nutr. 17, 57 (1965).

    PubMed  CAS  Google Scholar 

  60. J. A. Halstead and J. C. Smith,Gastroenterology 67, 193 (1974).

    Google Scholar 

  61. R. E. Burch, H. K. Hahn, and J. F. Sullivan,Clin. Chem. 21, 501 (1975).

    PubMed  CAS  Google Scholar 

  62. M. Castro-Magana, P. J. Collip, S. Y. Chen, S. Amin, and V. T. Maddaiah,Pediat. Res. 12, 515 (1978).

    Article  Google Scholar 

  63. A. Flynn, S. S. Martier, R. J. Sokol, N. L. Golden, B. C. DelVillano,Lancet 1, 572 (1981).

    Article  PubMed  CAS  Google Scholar 

  64. R. A. Mendelson and A. M. Huber, inCurrents in Alcoholism: Recent Advances in Research and Treatment, M. Galanter, ed., Grune and Stratton, New York, 1980, p. 39.

    Google Scholar 

  65. F. K. Ghishan, R. Patwardhan, and H. L. Greene,J. Lab. Clin. Med. 100, 45 (1982).

    PubMed  CAS  Google Scholar 

  66. G. I. Henderson, A. M. Hoyumpa, and C. Schenker,Alcoholism: Clin. Exp. Res. 3, 99 (1979).

    Article  CAS  Google Scholar 

  67. I. E. Dreosti, S. J. Manuel, and R. A. Buckley,Br. J. Nutr. 48, 205 (1982).

    Article  PubMed  CAS  Google Scholar 

  68. R. A. Ruth and S. K. Goldsmith,J. Nutr 111, 2034 (1981).

    PubMed  CAS  Google Scholar 

  69. S. I. Miller, B. C. DelVillano, A. Flynn, and M. Krumhansl,Pharmacol. Biochem. Behav. 18, 311 (1983).

    Article  PubMed  CAS  Google Scholar 

  70. I. E. DreostiJ. Comm. Nutr. in press.

  71. I. E. Dreosti,Med. J. Aust. 2, 3 (1981).

    PubMed  CAS  Google Scholar 

  72. J. F. Sullivan, M. M. Jetton, H. K. J. Hahn, and R. E. Burk,Am. J. Clin. Nutr. 33, 51 (1980).

    PubMed  CAS  Google Scholar 

  73. I. E. Dreosti and I. R. Record,Br. J. Nutr. 41, 399 (1979).

    Article  PubMed  CAS  Google Scholar 

  74. C. L. Keen, T. Tamura, B. Lonnerdal, L. S. Hurley, and C. H. Halstead,Am. J. Clin. Nutr. 35, 836 (1982).

    Google Scholar 

  75. H. P. Misra and L. D. Gorsky,J. Biol. Chem. 256, 9994 (1981).

    PubMed  CAS  Google Scholar 

  76. J. W. Hanson, K. L. Jones, and D. W. Smith,JAMA 235 1458 (1976).

    Article  PubMed  CAS  Google Scholar 

  77. H. H. Sandstead, G. J. Fosmire, J. M. McKenzie, and E. S. Halas,Fed. Proc. 34, 86 (1975).

    PubMed  CAS  Google Scholar 

  78. I. E. Dreosti, inNeurobiology of the Trace Elements, I. E. Dreosti and R. M. Smith, eds., Humana Press, Clifton NJ, 1983, p. 135.

    Chapter  Google Scholar 

  79. E. W. Walker, D. E. Barnes, S. F. Zornatzer, B. E. Hunter, and P. Kubanic,Science 209 711 (1980).

    Article  PubMed  CAS  Google Scholar 

  80. J. R. West, C. A. Hodges, and A. C. Black,Science 211, 957, (1981).

    Article  PubMed  CAS  Google Scholar 

  81. S. J. Buell, G. J. Fosmire, D. A. Ollorich, and H. H. Sandstead,Exp. Neurol. 54, 199 (1977).

    Article  Google Scholar 

  82. I. E. Dreosti, S. J. Manuel, R. A. Buckley, F. J. Fraser, and I. R. Record,Life Sci. 28, 2133 (1981).

    Article  PubMed  CAS  Google Scholar 

  83. G. W. Hesse,Science 205, 1005 (1979).

    Article  PubMed  CAS  Google Scholar 

  84. T. McLardy,Orthomol. Psychiatry 4, 32 (1975).

    Google Scholar 

  85. A. Sahgal,Trends Neurosci. 3 116 (1980).

    Article  Google Scholar 

  86. I. E. Dreosti and F. J. Fraser, inNeurobiology of Zinc, Vol. 2, C. J. Frederickson, G. A. Howell, and E. J. Kasarskis, eds., Liss, New York, 1984, p. 223.

    Google Scholar 

  87. J. C. Kawamoto and E.S. Hallas, inNeurobiology of Zinc, Vol. 2, C. J. Frederickson, G. A. Howell, and E. J. Kasarskis, eds., Liss, New York, 1984, p. 33.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dreosti, I.E., Record, I.R. & Manuel, S.J. Zinc deficiency and the developing embryo. Biol Trace Elem Res 7, 103–122 (1985). https://doi.org/10.1007/BF02916569

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02916569

Index Entries

Navigation