Progress Toward Identifying Causes of Maldevelopment Induced in Xenopus by Pond Water and Sediment Extracts From Minnesota, Usa

Abstract

In previously conducted laboratory studies with the South African clawed frog (Xenopus laevis), pond water and sediment samples collected from various sites in Minnesota, USA, were demonstrated to have the potential to induce a variety of developmental abnormalities, including early embryo-larval maldevelopment, abnormal limb development, and disruption of metamorphosis. The results of exposure of X. laevis to suspect pond water and sediment samples supported the hypothesis that these samples were capable of inducing these abnormalities as the result of either the presence of developmental toxicants or the absence of essential micronutrients. Physicochemical characterization of the causes of abnormal frog embryo-larval and limb development were performed using the frog embryo teratogenesis assay-Xenopus (FETAX). Specific compounds were subsequently identified within the complex mixture fractions and tested by dilution in a control solution and native reference water using both the 4- and 30-d treatment protocols. Results from these studies suggested that a complex mixture of both naturally occurring and man-made compounds was primarily responsible for the effects observed in X. laevis. The potency of several compounds was also enhanced by the site water, thus indicating that the water matrix deserves consideration as a contributing factor for both laboratory and field studies.

Effect of Sulfometuron Methyl and Nicosulfuron on Development and Metamorphosis in Xenopus Laevis: Impact of Purity

“…Thus, based on this study, longer-term developmental processes seemingly are more likely to be affected by sulfonylurea herbicides. These findings are not necessarily surprising, because the amphibian endocrine system has recently been identified as a significant target for many environmental toxicants [3,[22][23][24]. The sensitivity of this stage of development can be attributed to the importance and myriad of functions the endocrine system, particularly the thyroid axis, plays during metamorphosis.…”

“…Because the thyroid axis, including thyroid hormones and thyroid hormone receptors, is of paramount importance in the maturation of frogs, thyroid dysfunction is capable of producing a myriad of deleterious effects. For example, resorption of the tail, secondary anatomical characteristics, morphogen activity, development of the limbs, and maturation of juvenile skin to that of adult frogs are at least partially controlled by the thyroid axis [3,[22][23][24]. Thus, the possibility of larvae with severe thyroid dysfunction surviving in the wild is slim.…”

“…The present study indicated that the tail resorption assay was capable of detecting chemicals that may disrupt the thyroid axis, but T 4 coadministration studies and biochemical analysis are required to confirm whether the effects are directly the result of thyroid inhibition or are due to other indirect mechanisms. Emerging data that begin to demonstrate the correlation between antithyroid effects and limb maldevelopment [3,[22][23][24] have in-teresting ramifications concerning amphibians found in the environment with limb malformations. Considering that retinoic acid is the primary morphogen responsible for limb development and that thyroid hormones partially control expression of retinoic acid receptor metabolism [22,25], a direct biochemical link may exist and warrants further study.…”

Effect-directed analysis: a promising tool for the identification of organic toxicants in complex mixtures?

“…Test systems successfully applied in EDA were presented including the frog embryo teratogenesis assay with Xenopus laevis (FETAX) [106], fish embryo test applying eggs of Salmo trutta [107] and Oryzias latipes [108].…”

“…in Canada [134]) raised the requirement to identify the causing compounds. This was attempted by Fort et al [106] who identified and qualitatively confirmed propylthiourea, the carbamate fungicide maneb and the pyrethroid insecticide permethrin as important contributors to frog teratogenicity.…”