Skip to main content
SpringerLink
Log in

Chronic boron or copper deficiency induces limb teratogenesis in Xenopus

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

Abstract

Sets of adult male and female Xenopus laevis were administered a boron-deficient (−B) diet under low-boron culture conditions, a boron-supplemented (+B) diet under ambient boron culture conditions, a copper-deficient (−Cu) diet under low-copper culture conditions, or a copper-supplemented (+Cu) diet under ambient copper culture conditions, for 120 d. Adults from each group were subsequently bred, and the progeny were cultured and bred. Results from these studies indicated that although pronounced effects on adult reproduction and early embryo-larval development were noted in the −B F1 generation, no effects on limb development were observed. No significant effects on reproduction, early embryogenesis, or limb development were noted in the +B group, irrespective of generation. Highly specific forelimb and hindlimb defects, including axial flexures resulting in crossed limbs and reduction deficits, were observed in −B F2 larvae, but not in the +B F2 larvae. As was noted in the boron-deficiency studies, significant effects on reproduction and early embryo development were observed in the −Cu F1 generation, but not in the +Cu F1 generation. Unlike the effects associated with boron deficiency, maldevelopment of the hindlimbs (32 responders, n=40) was found in the F1 generation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. C. L. Keen and S. Zidenberg-Cherr, Should vitamin-mineral supplements be recommended for all women with childbearing potential? Am. J. Clin. Nutr. 59, 532S-539S (1994).

    PubMed  CAS  Google Scholar 

  2. G. M. Shaw, D. Schaffer, E. M. Velie, K. Morland, and J. A. Harris, Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects, Epidemiology 6, 219–226 (1995).

    Article  PubMed  CAS  Google Scholar 

  3. L. S. Hurley and C. L. Keen, Teratogenic effects of copper, in Teratogenic Effects of Copper, J. O. Nriagu, ed., Wiley, New York, pp. 33–56 (1979).

    Google Scholar 

  4. C. L. Keen, Teratogenic effects of essential trace metals: deficiencies and excesses, in Teratogenic Effects of Essential Trace Metals: Deficiencies and Excesses, L. W. Chang, L. Megos, and T. Suzuki, eds., CRS Lewis Publishers, New York, pp. 977–1001 (1996).

    Google Scholar 

  5. C. L. Keen, J. Y. Uriu-Hare, S. N. Hawk, M. A. Janowski, C. L. Kwik-Uribe, and R. B. Rucker, Effect of Cu deficiency of prenatal development and pregnancy outcome, Am. J. Clin. Nutr. 67(Suppl.), 10035–10115 (1998).

    Google Scholar 

  6. S. N. Hawk, J. Y. Uriu-Hare, G. P. Daston, M. A. Jankowski, C. Kwik-Uribe, R. B. Rucker, et al., Rat embryos cultured under copper-deficient conditions develop abnormally and are characterized by an impaired oxidant defense system, Teratology 57(6), 310–320 (1998).

    Article  PubMed  CAS  Google Scholar 

  7. G. D. Mieden, C. L. Keen, L. S. Hurley, and N. W. Klein, Effects of whole rat embryos cultured on serum from zinc- and copper-deficient rats, J. Nutr. 116, 2424–2431 (1986).

    PubMed  CAS  Google Scholar 

  8. D. J. Fort, E. L. Stover, C. M. Lee, and W. J. Adams, Adverse developmental and reproductive effects of copper deficiency in Xenopus laevis, Biol. Trace Element Res. 77, 159–172 (2000).

    Article  CAS  Google Scholar 

  9. J. N. Dumont, T. W. Schultz, M. Buchanan, and G. Kai, Frog embryo teratogenesis assay: Xenopus—a short-term assay applicable to complex mixtures, in Symposium on the Application of Short-Term Bioassays in the Analysis of Complex Environmental Mixtures II, M. D. Waters, S. S. Sandhu, J. Lewtas, L. Claxton, N. Chernoff, and S. Nesnow, eds., Plenum, New York, pp. 393–405 (1983).

    Google Scholar 

  10. D. J. Fort, D. A. Dawson, and J. A. Bantle, Evaluation of the development of a metabolic activation system for the frog embryo teratogenesis assay: Xenopus (FETAX), Teratogen. Carcinogen. Mutagen. 8, 251–263 (1988).

    Article  CAS  Google Scholar 

  11. D. J. Fort, B. L. James, and J. A. Bantle, Evaluation of the developmental toxicity of five compounds with the frog embryo teratogenesis assay: Xenopus (FETAX), J. Appl. Toxicol. 9, 377–389 (1989).

    Article  PubMed  CAS  Google Scholar 

  12. D. A. Dawson and T. S. Wilke, Joint toxic action of binary mixtures in osteolathyrogens at malformation inducing concentrations for Xenopus embryos, J. Appl. Toxicol. 11, 415–424 (1991).

    Article  PubMed  CAS  Google Scholar 

  13. D. J. Fort and J. A. Bantle, Use of frog embryo teratogenesis assay—Xenopus (FETAX) and an exogenous metabolic activation system to evaluate the developmental toxicity of diphenylhydantoin, Fundam. Appl. Toxicol. 14, 720–733 (1990).

    Article  PubMed  CAS  Google Scholar 

  14. D. J. Fort, T. L. Propst, E. L. Stover, P. L. Strong, and F. J. Murray, Adverse reproductive and developmental effects in Xenopus from insufficient boron, Biol. Trace Element Res. 66, 237–259 (1998).

    CAS  Google Scholar 

  15. R. I. Rowe, C. Bouzan, S. Nabili, and C. D. Eckhert, The response of trout and zebrafish embryos to low and high boron concentrations is U-shaped. Biol. Trace Element Res. 66, 261–270 (1998).

    CAS  Google Scholar 

  16. D. J. Fort, T. L. Propst, E. L. Stover, P. L. Strong, and F. J. Murray, Adverse effects from low dietary and environmental boron exposure on reproduction, development, and maturation in Xenopus laevis, J. Trace Element Exp. Med. 12(3), 175–185 (1999).

    Article  CAS  Google Scholar 

  17. D. J. Fort, E. L. Stover, P. L. Strong, F. J. Murray, and C. L. Keen, Chronic feeding of a low-boron diet results in adverse reproductive and developmental effects in Xenopus laevis, J. Nutr. 129(11), 2055–2060 (1999).

    PubMed  CAS  Google Scholar 

  18. D. J. Fort, E. L. Stover, P. L. Strong, and F. J. Murray, The effect of boron deprivation on reproductive parameters in Xenopus laevis, J. Trace Element Exp. Med. 12(3), 187–204 (1999).

    Article  CAS  Google Scholar 

  19. D. A. Dawson and J. A. Bantle, Development of a reconstituted water medium and initial validation of FETAX, J. Appl. Toxicol. 7, 237–244 (1987).

    Article  PubMed  CAS  Google Scholar 

  20. ASTM, Standard Guide for Conducting the Frog Embryo Teratogenesis Assay—Xenopus (FETAX), E1439-98, American Society for Testing and Materials, Philadelphia (1998).

    Google Scholar 

  21. C. D. Hunt, Biochemical effects of physiological amounts of dietary boron, J. Trace Element Exp. Med. 9, 185–213 (1996).

    Article  CAS  Google Scholar 

  22. C. D. Hunt, Dietary boron deficiency and supplementation, in Trace Elements in Laboratory Rodents, R. R. Watson, ed., CRC, Boca Raton, FL, pp. 229–253 (1996).

    Google Scholar 

  23. D. J. Fort, J. R. Rayburn, D. J. DeYoung, and J. A. Bantle, Assessing the efficacy of an Aroclor 1254-induced exogenous metabolic activation system for FETAX, Drug Chem. Toxicol. 14, 143–161 (1991).

    PubMed  CAS  Google Scholar 

  24. D. J. Fort, J. R. Rayburn, and J. A. Bantle, Mechanisms of acetaminophen-induced developmental toxicity in vitro, Drug Chem. Toxicol. 15, 329–350 (1992).

    PubMed  CAS  Google Scholar 

  25. D. J. Fort and E. L. Stover, Effect of low-level copper and pentachlorophenol exposure on various early life stages of Xenopus laevis, in Environmental Toxicology and Risk Assessment: Biomarkers and Risk Assessment—Fifth Volume, D. A. Bengston and D. S. Henshel, eds., ASTM STP 1306, American Society for Testing and Materials, Philadelphia, pp. 188–203 (1996).

    Google Scholar 

  26. D. J. Fort and E. L. Stover, Development of short-term, whole embryo assays to evaluate detrimental effects on amphibian limb development and metamorphosis using Xenopus laevis, in Environmental Toxicology and Risk Assessment: Modeling and Risk Assessment—Sixth Volume, F. J. Dwyer, T. R. Doane, and M. L. Hinman, eds., ASTM STP 1317, American Society for Testing and Materials, Philadelphia, pp. 376–390 (1997).

    Google Scholar 

  27. S. E. Long and T. D. Martin, Methods for the Determination of Metals in Environmental Samples, U.S. Environmental Protection Agency, EMSL, Cincinnati, OH, pp. 83–122 (1991).

    Google Scholar 

  28. D. A. Dawson and J. A. Bantle, Coadministration of methylxanthines and inhibitor compounds potentiates teratogenicity in Xenopus embryos, Teratology 35, 221–227 (1988).

    Article  Google Scholar 

  29. D. J. Fort, T. L. Propst, E. L. Stover, J. C. Helgen, R. Levey, K. Gallagher, et al., Effect of selected pond water, sediment, and sediment extracts from the states of Minnesota and Vermont on early development and metamorphosis in Xenopus, Environ. Toxicol. Chem. 18(10), 2305–2315 (1999).

    Article  CAS  Google Scholar 

  30. T. W. Schultz and T. S. Raney, Structure-activity relationships for osteolathyrism: II. Effects of alkylsubstituted acid hydrazides, Toxicology 53, 147–159 (1988).

    Article  PubMed  CAS  Google Scholar 

  31. R. W. Schultz, T. S. Raney, G. W. Riggin, and M. Cajinda-Quezada, Structure-activity relationships for osteolathyrism: I. Effects of altering semicarbizide structure, Trans. Am. Microsc. Soc. 107, 113–126 (1988).

    Article  CAS  Google Scholar 

  32. D. A. Dawson, D. J. Fort, G. L. Smith, D. L. Newell, and J. A. Bantle, Comparative evaluation of the developmental toxicity of nicotine and cotinine with FETAX, Teratogen. Carcinogen. Mutagen. 8, 329–388 (1988).

    Article  CAS  Google Scholar 

  33. D. J. Fort, R. L. Rogers, H. F. Copley, L. Bruning, E. L. Stover, J. Helgen, et al., Progress toward identifying causes of mal-development induced in Xenopus by pond water and sediment extracts from Minnesota, Environ. Toxicol. Chem. 18(10), 2316–2324 (1999).

    Article  CAS  Google Scholar 

  34. M. Maden and J. Corcoran, Role of thyroid hormone and retinoid receptors in the homeotic transformation of tails into limbs in frogs, Dev. Genet. 19(1), 85–93 (1996).

    Article  PubMed  CAS  Google Scholar 

  35. T. Takeda, T. Nagasawa, T. Miyamoto, K. Hashizume, and L. J. DeGroot, The function of retinoid X receptors on negative thyroid hormone response elements, Mol. Cell. Endocrinol. 128, 85–96 (1997).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Stover Group, 74074, Stillwater, OK

    Douglas J. Fort, Enos L. Stover, Robert L. Rogers, Holly F. Copley, Lisa A. Morgan & Elicia R. Foster

Authors
  1. Douglas J. Fort
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enos L. Stover
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert L. Rogers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Holly F. Copley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lisa A. Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elicia R. Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fort, D.J., Stover, E.L., Rogers, R.L. et al. Chronic boron or copper deficiency induces limb teratogenesis in Xenopus . Biol Trace Elem Res 77, 173–187 (2000). https://doi.org/10.1385/BTER:77:2:173

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:77:2:173

Index Entries

Search

Navigation