H2O2 induces abnormal tail flexure in Xenopus embryos: similarities with paraquat teratogenic effects

BACKGROUND: As previously shown, Paraquat (PQ) treatments of Xenopus developing embryos mainly induce 6 characteristic developmental alteration we named "abnormal tail flexure." PQ oxidative activity has been indicated as the cause of this malformation. Since PQ evokes reactive oxygen species (ROS), among which hydroxyl radicals (OH center dot), and H2O2 can be converted to (OH center dot) via Fenton reaction, we compared here the lethal and teratogenic potentials of both oxidants by using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX), in order to grasp eventual similarities in their teratogenic activity. METHODS: Xenopus embryos were exposed, from stage 8 to stage 47, at 368, 491, 612, and 735 PM H2O2 and 0.388 mu M PQ. The probit analysis of H2O2 mortality and malformed larva percents gave a 598.82 mu M Lethal Concentration 50% (LC50) and 536.04 mu M Teratogenic Concentration 50% (TC50) from which a 1.11 Teratogenic Index (T.I.) has been calculated. This T.I. value should allow the classification of H2O2 as a non-teratogenic compound. RESULTS: A comparison of H2O2 mortality and malformed larva percents with those obtained from PQ exposure showed the higher embryotoxicity of PQ, but, markedly, both compounds mainly induced the "abnormal tail flexure." Histological analysis of both H2O2 and PQ malformed embryo tails showed a similar distorted morphology of both somites and myocytes. Some of muscle cells were necrotic and affected by an apical enlargement as well as a detachment from the connective tissue of intersomitic boundaries. CONCLUSIONS: In our opinion, both of the tested chemicals likely weaken the mechanical bridge connecting the myocyte contractile apparatus to the extracellular matrix, therefore causing the detachment of some of tail myocytes from their connectival septum as well as their apical enlargement. This could lead to the unbalance of tail tensional forces and, in turn, to the appearance of the "abnormal tail flexure."