title: Common deregulated gene expression profiles and morphological changes in developing zebrafish larvae exposed to environmental-relevant high to low concentrations of glucocorticoids.
abstract: Synthetic glucocorticoids have been detected in environmental waters and their biological potency have raised concerns of their impact on aquatic vertebrates especially fish. In this study, developing zebrafish larvae exposed to representative glucocorticoids (dexamethasone, prednisolone and triamcinolone) at 50 pM to 50 nM from 3 h post-fertilisation to 5 days post-fertilisation were investigated. Microarray analysis identified 1255, 1531, and 2380 gene probes, which correspondingly mapped to 660, 882 and 1238 human/rodent homologs, as deregulated by dexamethasone, prednisolone and triamcinolone, respectively. A total of 248 gene probes which mapped to 159 human/rodent homologs were commonly deregulated by the three glucocorticoids. These homologs were associated with over 20 molecular functions from cell cycle to cellular metabolisms, and were involved in the development and function of connective tissue, nervous, haematological, and digestive systems. Glucocorticoid receptor signalling, NRF2-mediated oxidative stress response and RAR signalling were among the top perturbed canonical pathways. Morphological analyses using four transgenic zebrafish lines revealed that the hepatic and endothelial-vascular systems were affected by all three glucocorticoids while nervous, pancreatic and myeloid cell systems were affected by one of them. Quantitative real-time PCR detected significant change in the expression of seven genes at 50 pM of all three glucocorticoids, a concentration comparable to total glucocorticoids reported in environmental waters. Three genes (cry2b, fbxo32, and klhl38b) responded robustly to all glucocorticoid concentrations tested. The common deregulated genes with the associated biological processes and morphological changes can be used for biological inference of glucocorticoid exposure in fish for future studies.
authors.affiliation: NUS Environmental Research Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Chen
authors.affiliation: NUS Environmental Research Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore; Department of Biological Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biological Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Singapore.
authors.forename: Eric Chun Yong
authors.initials: ECY
authors.lastname: Chan
authors.affiliation: University of Arizona, 1133 E. James E. Rogers Way, Harshbarger 108, Tucson, AZ 85721-0011, USA.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Snyder
authors.affiliation: NUS Environmental Research Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore; Department of Biological Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore. Electronic address: dbslsh@nus.edu.sg.
authors.forename: Siew Hong
authors.initials: SH
authors.lastname: Lam
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000254:growth & development; D003907:Dexamethasone / Q000737:chemistry*; D004777:Environment; D004784:Environmental Monitoring / Q000379:methods*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000737:chemistry*; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D015398:Signal Transduction; D059467:Transcriptome; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D005938:Glucocorticoids; D029961:Zebrafish Proteins; D003907:Dexamethasone
keywords: Environmental-relevant; Glucocorticoids; Microarray; Transcriptome; Zebrafish