Abstract
The effect of copper (Cu) deficiency on the reproduction and development in Xenopus laevis was evaluated, culminating in the development of a defined concentration-response relationship. Separate groups of four adult frog pairs were fed one of three diets for 28 d: (1) low-copper (−Cu); (2) copper supplemented (+Cu); and (3) ASTM standard beef liver and lung (BLL). Embryos collected from frogs administered the −Cu diet had markedly decreased egg masses and viability rates and an increased rate of necrosis when compared to the other dietary treatments. Malformations in −Cu larvae included maldevelopment of the heart, eye, craniofacial region, brain, and notochord. Larvae from adults administered the −Cu diet showed delayed abnormal hindlimb development, characterized as selective reductive deficiencies distal to the femur, with poor cartilaginous development. A U-shaped dose-response curve characteristic of nutritional essentiality was developed for Cu. Overall, these studies indicated that embryos produced from frogs administered a −Cu diet are substantially less viable than embryos from frogs administered a +Cu or copper-adequate (BLL) diet.
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References
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).
G. M. Shaw, D. Schaffer, E. M. Velie, K. Morland, and J. A. Harris, Periconception vitamin use, dietary folate, and the occurrence of neural tube defects, Epidemiology 6, 219–226 (1995).
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., CRC Lewis Publishers, New York, pp. 988–1001 (1996).
C. L. Keen, J. Y. Uriu-Hare, S. N. Hawk, M. A. Jankowski, C. L. Kwik-Uribe, and R. B. Rucker, Effect of Cu deficiency on prenatal development and pregnancy outcome, Am. J. Clin. Nutr. 67(Suppl), 10035–10115 (1998).
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).
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, 310–320 (1998).
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).
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).
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).
D. J. Fort and J. A. Bantle, Use of the 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).
D. J. Fort and J. A. Bantle, Analysis of the mechanism of isoniazid-induced developmental toxicity with the Frog Embryo Teratogenesis Assay—Xenopus (FETAX), Teratogen. Carcinogen. Mutagen. 10, 463–476 (1990).
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).
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).
G. Greenhouse, The evaluation of toxic effect of chemicals in fresh water by using frog embryos and larvae, Environ. Contam. Toxicol. 20, 93–95 (1978).
J. N. Dumont, T. W. Schultz, M. Buchanan, and G. Kao, Frog Embryo Teratogenesis Assay—Xenopus (FETAX): a short-term assay applicable to complex environmental mixtures, in Short-Term Bioassays in the Analysis of Complex Environmental Mixtures III, M. D. Waters, S. S. Sandhu, J. Lewtas, L. Claxton, N. Chernoff, and S. Nesnow, eds., Plenum, New York, pp. 393–405 (1983).
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).
J. A. Bantle, D. A. Dawson, and D. J. Fort, Identification of developmental toxicants using the frog embryo teratogenesis assay—Xenopus (FETAX), Hydrobiologia 188/189, 577–585 (1989).
D. A. Dawson, D. J. Fort, D. L. Newell, and J. A. Bantle, Developmental toxicity testing with FETAX: evaluation of five validation compounds, Drug Chem. Toxicol. 12, 67–76 (1989).
J. A. Bantle, D. J. Fort, J. R. Rayburn, D. J. DeYoung, and S. J. Bush, Further validation of FETAX: evaluation of the development toxicity of five known mammalian teratogens and non-teratogens, Drug Chem. Toxicol. 13, 267–283 (1990).
D. J. DeYoung, J. A. Bantle, and D. J. Fort, Assessment of the developmental toxicity of ascorbic acid, sodium selenate, coumarin, serotonin and 13-cis retinoic acid using FETAX, Drug Chem. Toxicol. 14, 127–143 (1991).
ASTM, Standard Guide for Counducting the Frog Embryo Teratogenesis Assay—Xenopus (FETAX), E1439-91, American Society for Testing and Materials, Philadelphia (1991).
J. A. Bantle, J. N. Dumont, R. A. Finch, and G. Linder, Atlas of Abnormalities: A Guide for the Performance of FETAX, Oklahoma State University Press, Stillwater (1991).
T. D. Sabourin and R. T. Faulk, Comparative evaluation of a short-term test for developmental effects using frog embryos, Branbury Report 26: Developmental Toxicology: Mechanisms and Risk, pp. 203–223 (1987).
C. L. Courchesne and J.A. Bantle, Analysis of the activity of DNA, RNA, and protein synthesis inhibitors on Xenopus embryo development, Teratogen. Carcinogen. Mutagen. 5, 177–193 (1985).
J. N. Dumont, T. W. Schultz, and R. G. Epler, The response of the FETAX model to mammalian teratogens, Teratology 27, 39a (1983).
P. E. Mirkes, Cyclophosphamide teratogenesis: a review, Teratogen. Carcinogen. Mutagen. 5, 75–88 (1985).
J. A. Bantle and D. A. Dawson, Uninduced rat liver microsomes as an in vitro metabolic activation system for the Frog Embryo Teratogenesis Assay—Xenopus (FETAX), in Proceedings of the 10th Aquatic Toxicology and Hazard Assessment, W. J. Adams, G. A. Chapman, and W. G. Landis, eds., ASTM 971, American Society for Testing and Materials, Philadelphia, pp. 316–326 (1987).
J. A. Bantle, D. J. Fort, and D. A. Dawson, Bridging the gap from short-term teratogenesis assays to human health hazard assessment by understanding common modes of teratogenic action, in Proceedings of the 12th Aquatic Toxicology and Hazard Assessment, U. M. Cowgill and L. R. Williams, eds., ASTM STP 1027, American Society for Testing and Materials, Philadelphia, pp. 46–58 (1988).
D. J. Fort and E. L. Stover, Effect of low-level copper and pentachlorophenol exposure on various early life stages of Xenopus laevis, in Proceedings of the Fifth Environmental Toxicology and Risk Assessment, D. A. Bengton and D. S. Henshel, eds., ASTM STP 1306, American Society for Testing and Materials, Philadelphia, pp. 188–203 (1996).
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 Proceedings of the Sixth Environmental Toxicology and Risk Assessment, 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).
D. J. Fort, T. L. Propst, T. Schetter, and E. L. Stover, Teratogenic effects of insufficient boron, copper and zinc in Xenopus, Teratology, 57, 104 (1998).
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).
D. J. Fort, T. L. Propst, 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, J. Nutr. 129(11), 2055–2060 (1999).
D. J. Fort, T. L. Propst, E. L. Stover, F. J. Murray, and P. L. Strong, Adverse effects of low boron exposure on reproduction, development and maturation in Xenopus laevis, J. Trace Element Exp. Med. 11, 374–375 (1998).
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Fort, D.J., Stover, E.L., Lee, C.M. et al. Adverse developmental and reproductive effects of copper deficiency in Xenopus laevis . Biol Trace Elem Res 77, 159–172 (2000). https://doi.org/10.1385/BTER:77:2:159
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DOI: https://doi.org/10.1385/BTER:77:2:159