Thyroid Hormone Disruptors Interfere with Molecular Pathways of Eye Development and Function in Zebrafish

Abstract

The effects of thyroid hormone disrupting chemicals (THDCs) on eye development of zebrafish were investigated. We expected THDC exposure to cause transcriptional changes of vision-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Zebrafish were exposed from 0 to 5 days post fertilization (dpf) to either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or tetrabromobisphenol-A (TBBPA), which interacts with thyroid hormone receptors. Full genome microarray analyses of RNA isolated from eye tissue revealed that the number of affected transcripts was substantially higher in PTU- than in TBBPA-treated larvae. However, multiple components of phototransduction (e.g., phosphodiesterase, opsins) were responsive to both THDC exposures. Yet, the response pattern for the gene ontology (GO)-class “sensory perception” differed between treatments, with over 90% down-regulation in PTU-exposed fish, compared to over 80% up-regulation in TBBPA-exposed fish. Additionally, the reversibility of effects after recovery in clean water for three days was investigated. Transcriptional patterns in the eyes were still altered and partly overlapped between 5 and 8 dpf, showing that no full recovery occurred within the time period investigated. However, pathways involved in repair mechanisms were significantly upregulated, which indicates activation of regeneration processes.

The Role of Estrogen and Thyroid Hormones in Zebrafish Visual System Function

“…Exposure to PTU from 0 to 5 dpf reduced eye size in zebrafish larvae and alters optokinetic responses ( Baumann et al, 2016 ; Gothie et al, 2019 ); effects correlated with PTU-induced downregulation of TR expression ( Baumann et al, 2016 ). Subsequent microarray analysis revealed PTU exposure caused downregulation of phototransduction-related genes coding for opsins, phosphodiesterase, and arrestin ( Baumann et al, 2019 ). In fact, of the genes involved in sensory perception, expression of >90% were found to be downregulated by PTU.…”

“…In fact, of the genes involved in sensory perception, expression of >90% were found to be downregulated by PTU. The number of downregulated genes remained high when measured after a 3-day removal from treatment, though the levels of downregulation were less ( Baumann et al, 2019 ), suggesting differential sensitivity to specific genes and long-term impacts of exposure.…”

“…The effect of TBBPA exposure on expression of specific genes was variable ( Baumann et al, 2016 ), consistent with agonistic and/or antagonistic effects of this compound. Indeed, though opsin expression was upregulated after a 5-day exposure to TBBPA (from 0 to 5 dpf), overall TBBPA exposure caused more general effects than PTU ( Baumann et al, 2019 ). However, compared to PTU-induced downregulation of genes involved in sensory perception, >80% were upregulated by TBBPA.…”

Anthropogenic stressors impact fish sensory development and survival via thyroid disruption

“…Thyroid hormones are important for regulating sensory development in teleost fishes 11,14,36,38 , and our results provide insights into the role they play in this development during recruitment. A. triostegus exhibits an enclosed nose (Supplementary Fig.…”

Feasibility of using interspecies relationships for integration of human and environmental hazard assessment

“…Like in amphibians and mammals, also in teleosts the HPT axis is required for normal development and metamorphosis (Carr and Patiño 2011). Several studies already have shown that fish are sensitive to thyroid active substances (Baumann et al 2019;Dang and Kienzler 2019;Stinckens et al 2016). From a risk assessment point of view it would be of interest to know whether the results of (chronic) toxicity tests with fish, which are a standard requirement in various regulatory frameworks, cover the sensitivity of amphibians as well as aquatic species in general.…”