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Studying Neurobehavioral Effects of Environmental Pollutants on Zebrafish Larvae
Published on: February 5, 2020
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Organophosphate esters cause thyroid dysfunction via multiple signaling pathways in zebrafish brain.
Zhenfei Yan1,2, Chenglian Feng1, Xiaowei Jin3
1State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China.
Environmental Science and Ecotechnology
|September 26, 2022
Summary
Organophosphate esters (OPEs) act as environmental thyroid hormones (THs), disrupting zebrafish growth by inhibiting TH transport and synthesis. These compounds interfere with crucial signaling pathways, impacting endocrine functions and lipid metabolism.
Area of Science:
- Environmental Science
- Endocrinology
- Toxicology
Background:
- Organophosphate esters (OPEs) are prevalent environmental contaminants.
- OPEs are known to interfere with thyroid hormone (TH) endocrine signaling.
- The precise mechanisms of OPEs' disruption of TH pathways remain unclear.
Purpose of the Study:
- To elucidate the mechanisms by which OPEs disrupt thyroid hormone signaling pathways.
- To establish OPEs as environmental thyroid hormones that inhibit zebrafish growth.
- To investigate OPEs' interactions with TH transport proteins and their effects on TH synthesis and signaling.
Main Methods:
- In vivo, in vitro, and in silico experiments were conducted.
- OPEs' binding to transthyretin (TTR) and thyroxine-binding globulin was assessed.
- Zebrafish growth inhibition and GH3 cell proliferation were measured following OPEs exposure.
- Gene expression analysis was performed using GO and KEGG databases.
Main Results:
- OPEs competitively inhibit TH by binding to TTR and thyroxine-binding globulin, affecting TH transport across the blood-brain barrier.
- OPEs significantly inhibited GH3 cell proliferation and zebrafish growth.
- Chronic OPEs exposure interfered with TH synthesis by affecting thyroperoxidase and thyroglobulin.
- Signaling pathways related to thyroid endocrine function, lipid metabolism, and neuroactive ligand-receptor interactions were modulated by OPEs.
Conclusions:
- OPEs function as environmental thyroid hormones, disrupting TH signaling and inhibiting zebrafish growth through multiple pathways.
- OPEs interfere with TH transport, synthesis, and receptor-ligand interactions.
- This study provides a comprehensive understanding of OPEs' endocrine-disrupting mechanisms in thyroid pathways.
Keywords:
AChE, acetylcholinesteraseANOVA, analysis of varianceBCF, bioconcentration factorBFR, brominated flame retardantCD-FBS, charcoal-dextran-treated fetal bovine serumCDP, cresyl diphenyl phosphateCompetitive inhibition assayDEG, differentially expressed geneDKA, β-diketone antibioticDMSO, dimethyl sulfoxideEAS, estrogenFBS, fetal bovine serumGAPDH, glyceraldehyde-3-phosphate dehydrogenaseGO, Gene OntologyHPLC-MS/MS, high-performance liquid chromatograph interfaced with a mass spectrometerHPT, hypothalamic–pituitary–thyroidHS, horse serumKEGG, Kyoto Encyclopedia of Genes and GenomesMAPK, mitogen-activated protein kinaseMolecular docking simulationNIS, Na+/I− symporterOD490, optical densityOPE, organophosphate esterOPFR, organophosphate flame retardantOrganophosphate esterP/S, penicillin–streptomycinPBDE, polybrominated diphenyl etherPBS, phosphate-buffered salineRIC20/50, concentration inhibiting 20%/50%T4, thyroxinTBG, thyroxine-binding globulinTCIPP, tris(2-chloroisopropyl) phosphateTDCIPP, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP)TDCIPP-d15, tris(1,3-dichloroisopropyl) phosphate-D15TG, thyroglobulinTH, thyroid hormoneTHR, thyroid hormone receptorTIPP, tris(isopropyl) phosphateTPHP, triphenyl phosphateTPO, thyroperoxidaseTRβ, thyroid hormone receptor βTTR, transthyretinThyroid endocrine functionTranscriptome sequencingandrogen, and steroidogenesiscga, glycoprotein hormoneqRT-PCR, quantitative real-time PCRtshβa, thyroid-stimulating hormone beta subunit a
