Toxicological Effects Of Cadmium On Intestinal And Skeletal Development And Hepatic Energy Metabolism In Bufo Gargarizans Tadpoles

Cadmium(Cd)is carcinogenic to human and it also has adverse effects on aquatic life such as amphibian larvae.Bufo gargarizans is widely distributed in eastern Asia and it very sensitive to environmental pollutants and the species was used as a model species for toxicological studies.In this study,B.gargarizans larvae were exposed to environmentally relevant Cd concentrations of 5,100 and 200 ?g L-1 from Gosner stage(Gs)26 to 42 of metamorphic climax about 6 weeks.In this study,we examined the effects of chronic cadmium exposure on gut microbiota changes and intestinal remodeling disruption,skeletal underdevelopment,liver cell apoptosis and hepatic energy metabolism disorder by disrupting thyroid hormone signaling in Bufo gargarizans larvae,the main findings were as follows:1.High cadmium(100 and 200 ?g L-1)exposure caused significant decrease of body length and weight but significant increase of intestinal length and weight.Moreover,severe histopathological damages including cytoplasmic damage,unclear cell boundary and nuclear pyknosis were induced by high Cd exposure.In addition,microbial communities in the gut of tadpoles in high cadmium exposure groups were remarkably different from those in control group.Unexpectedly,species diversity and richness were higher in the intestinal microbiota of 200 ?g L-1 cadmium exposure group.Furthermore,the abundance of prevalent phyla,families and genera of intestinal microbiota were changed by cadmium exposure.Meanwhile,cadmium exposure perturbed gut renewal functions and the relative mRNA expression of genes in canonical and non-canonical Wnt signaling pathway was seriously affected by high cadmium exposure.2.Thyroid structural injuries including follicle deformation,follicular epithelial cells disarrangement,follicular epithelial cell hypertrophy and exfoliation,and follicular atrophy were induced by high Cd exposure(100 and 200?g L-1).And in high concentration groups,the relative mRNA expression levels of deiodinase genes and thyroid hormone receptor genes in the skeleton were significantly downregulated.Moreover,tadpole skeleton including whole body,vertebrata,forelimb and hindlimb was developmentally delayed by high Cd exposure through downregulating the mRNA expressions of genes with skeletal ossification and growth pathway.Moreover,liver histopathological injuries were caused by high Cd exposure featured by hepatocytes malformation,nuclear degeneration and increasing melanomacrophage centers.Meanwhile,liver apoptosis rate showed on the rise in a dose-dependent way and Cd stimulated liver apoptosis by upregulating mRNA expressions of genes related to extrinsic and intrinsic apoptosis pathways.Cadmium induced hepatic energy metabolism disorder.High Cd caused hepatic glycometabolism disorder by decreasing the genetic expressions associated with glycolysis and mitochondrial oxidative phosphorylation.In addition,liver lipid metabolism was disrupted by high Cd exposure through downregulating mRNA levels of genes related to fatty oxidation and upregulating mRNA levels of genes related to fatty acid synthesis.We concluded that cadmium could be harmful to tadpole health by inducing intestinal histopathological damages,gut remodeling inhibition and intestinal microbiota alterations.And Cd did great harm to tadpole health by disturbing thyroid function,skeletal growth,liver cell apoptosis signaling and hepatic energy metabolism pathway.The research will contribute to the theoretical foundation on amphibian under cadmium pollution and it also provides many suggestions of amphibian ecological adaptations to environment with implications of wildlife conservation.It also contributes to detecting the potential bioindicator for environmental pollution monitoring.