Chronic Exposure To Cortisone Causes Thyroid Endocrine Disruption And Intestinal Flora Toxicity In Adult Zebrafis

Cortisone is a natural corticosteroid widely used in human and veterinary clinical therapy since its broad range of anti-inflammatory and immunosuppressive effects.Even though earlier studies have focused on the first identified sex hormones(e.g.,estrogens and androgens)and progestins,an increasing researcher has identified steroids as a potent class of endocrine disrupting chemicals,and the actual use of glucocorticoids whose concentration range from 0.3 ng/L to 473 ng/L in a variety of different aqueous environments is much greater than them,so it is important to understand the potential ecotoxicological risk of glucocorticoids in the aqueous environment.Even low levels of glucocorticoid exposure can cause a variety of toxic effects in aquatic animals.However,ecotoxicological studies on glucocorticoids have mainly focused on their reproductive toxicity,early embryonic developmental toxicity,and immune system disruptions,while relatively few studies have been conducted on the thyroid endocrine system and intestinal flora.Therefore,this study used cortisone to investigate the ecotoxicological effects on the thyroid endocrine system and intestinal flora of adult zebrafish under chronic exposure for60 days.The main results of the study are as follows:1.In this study,ecotoxicological risks were assessed in adult zebrafish with chronic exposure to cortisone.Endpoints included thyroid histological analysis,plasma thyroid hormone levels and TSH levels,transcript expression levels of genes in the HPT axis,Histological alterations in the retina and expression levels of genes related to the visual cycle and circadian rhythm in the eye,anxiety-like behavior analysis,genes related to the GABA synthesis pathway expression.The results showed that cortisone exposure in adult zebrafish interfered with the thyroid endocrine system and altered the transcriptional expression of genes in the visual cycle and circadian rhythm,which means affecting the normal physiological function of the eye and the induce anxiety in zebrafish.2.This study is the first to investigate the ecotoxicological effects of chronic exposure to glucocorticoids on the intestinal flora of adult zebrafish.A significant increase in body weight and length in zebrafish were found.RNA-seq analysis and 16 S r RNA highthroughput sequencing analysis were performed for this characterization.The transcriptomic data analysis showed that 3118 up-regulated genes and 4291 down-regulated genes between the control and high-concentration treatment groups.Chronic exposure to326.9 ng/L cortisone resulted in a significant decrease in the diversity of the zebrafish intestinal microbiota and a huge change in the composition,with the most significant difference at the phylum taxonomic level being Fusobacteria,while Cetobacterium was at the genus level.Functional predictions revealed that biosynthetic metabolic pathways including protein(amino acid biosynthesis),lipid(fatty acid and lipid biosynthesis)and sugar(carbohydrate biosynthesis)metabolism were significantly altered.