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STAGE-AND SPECIES-SPECIFIC DEVELOPMENTAL TOXICITY OF ALL-TRANS RETINOIC ACID IN FOUR NATIVE NORTH AMERICAN RANIDS AND XENOPUS LAEVIS
Citation:
Degitz, S J., P A. Kosian, E A. Makynen, K M. Jensen, AND G T. Ankley. STAGE-AND SPECIES-SPECIFIC DEVELOPMENTAL TOXICITY OF ALL-TRANS RETINOIC ACID IN FOUR NATIVE NORTH AMERICAN RANIDS AND XENOPUS LAEVIS. JOURNAL OF TOXICOLOGICAL SCIENCES 57:264-274, (2000).
Description:
Within the last decase there have been increasing reports of malformed amphibians across North America. Recently, it has been suggested that hindlimb malformations are a consequence of xenobiotic disruption of developmental pathways regulated by retinoids. To assess the validity of this hypothesis the developmental toxicity of all-trans retinoic acid (RA) was examined in four North American anurans: Rana pipiens, Rana sylvatica, Rana clamitans, Rana septenrionalis, and Xenopus laevis at several life stages. To determine the effects of RA on embryogenesis, mid-blastula stage embryos were exposed to 0, 6.25, 12.5, 25 and 50 ng RA/ml for 24 h. To evaluate the effects of RA on hindlimb development, early- and mid-limb bud stage tadpoles were exposed to RA concentrations of 0, 250, 500, 750, 1000 and as50 ng RA/ml for 24 h. Mid-blastula RA exposure resulted in a concentration-dependent increase in dysmorphogenesis and mortality in the three species examined (R. clamitans, R. septenrionalis and X. laevis). RA exposure at stage 51 in X. laevis and stage 28 in R. sylvatica resulted in a concentration-dependent increase in reductions and deletions of the hindlimb. However, RA was ineffective at inducine hindlimb abnormalities in stage 26 and 28 R. pipiens, stage 28 R. clamitans or stage 48 X. laevis tadpoles. These results indicate that mid-blastula stage embryos are more sensitive to RA-induced dysmorphogenesis and mortality than limb bud stage tadpoles. The significance of these findings are discussed in the context of the possible occurrence of retinoid minics in the environment.