Toxic Effects And Mechanisms Of Endocrine Disrupting Chemicals With Different Mode Of Actions On The Model Fish

The study of endocrine disruption is being increasingly conducted at the mRNA level of genes, as this approach can yield insight into the modes of action and mechanisms of toxicity. For the exposure is to multitude of chemicals simultaneous in reality, the effects of mixture of EDCs with different MOAs were of concern as well. In this study, the transcriptional responses of a set of genes involved in the hypothalamic-pituitary-gonadal (HPG; or HPG[L]-liver) axis of Japanese medaka were examined after treatment with two model anti-estrogens, letrozole (LET) and tamoxifen (TAM) at three concentrations (30,100and300μg/L). The results showed that LET and TAM produced distinct expression profiles in a complex tissue-and gender-specific manner, confirming that they exert their anti-estrogenic effects via different molecular mechanisms. Thereafter, the fish were exposed to binary mixture containing20ng/L EE2and30,100or300μg/L LET or TAM, and20ng/L EE2alone as the positive group for72hours. The exposure to the environmental estrogen EE2caused the induction of classic biomarkers of estrogen exposure, and the coexposure to LET or TAM may led to a complex effect of gene expression profiling. Overall, the experimental data provide the mechanistic information of anti-estrogenic chemicals or under the coexposure of estrogen with the complex effects. Accumulating evidence suggests that environmental endocrine disrupting chemicals may exert adverse effects on aquatic organisms via the modulation of immune competence. However, few studies have addressed the role of immune response gene transcript abundance in response to estrogen. In the present study, the ontogenetic expression of some immune-related genes were characterized during different developmental periods (from0to28d post-hatch [dph]) in Japanese medaka. Furthermore, the responses of these genes to natural estrogen (17β-estradiol [E2]) were evaluated. The results demonstrate a very different trend in gene expression in fish larvae exposed to E2when compared with the ontogenetic changes in control, suggesting that exposure to environmental chemicals with estrogenic activities have the ability of changing the immune related gene expression and interfere with immune system.