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Thyroid disruptors interfere with molecular pathways of eye development and function in zebrafish

ABSTRACT: Thyroid disruptors interfere with molecular pathways of eye development and function in zebrafish

PROVIDER: PRJNA497084 | ENA |

REPOSITORIES: ENA

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

Project description: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.

| S-EPMC6479403 | biostudies-literature

Thyroid disruptors interfere with molecular pathways of eye development and function in zebrafish

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-05-09 | GSE121338 | GEO

Characterization of Directly Regulated Thyroid Hormone Mediated Gene Expression Following Short-Term Perturbations in Thyroid Hormone Levels in Juvenile Mice

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Sexual dimorphism in the zebrafish eye proteins

Project description:The present study aims to apply a high-resolution and label-free proteomics approach to identify and quantify proteins in the eye of zebrafish. First, the results of the present study will provide a comprehensive list of proteins in the eye of zebrafish, and second, establish a platform based on sex-biased proteins that may offer clues to answer crucial questions such as sex-based differences in visual perception and impairments. Our results may improve the outcome of behavioural, developmental, toxicological, and medical experiments considering the zebrafish eye.

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Zebrafish early eye development

Project description:Gene expression profiling of zebrafish early eye development on 3 to 5 days post fertilization (dpf)

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Characterization of Directly Regulated Thyroid Hormone Mediated Gene Expression Following Short-Term Perturbations in Thyroid Hormone Levels in Juvenile Mice

Project description:We investigated the effects of thyroid hormone disruptions on gene expression in juvenile mice liver to develop a stronger understanding of the mechanisms by which thyroid disrupting chemicals impair development. Gene expression was examined by hybridization of hepatic RNA to Agilent mouse microarrays for hyper-, hypo-, hypo-replacement (hypo+) and euthyroid animals. Keywords: Toxicogenomics, biomarkers of thyroid disruptors Hypothyroidism was induced from post natal day (PND) 13 to 15 by adding model thyroid toxicants methimazole and sodium perchlorate to drinking water of pregnant females. Hyperthyroidism was induced by intraperitoneal injections (i.p.) of THs at PND 15, 4 hours before decapitation and tissue collection. For the hypothyroid/replacement group; dams were provided with drinking water for 3 days (PND 13 to 15), containing a mixture of methimazole/sodium perchlorate. Pups then received intraperitoneal injections of thyoid hormones on PND 15, 4 hours before decapitation and tissue collection.

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Zebrafish early eye development

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Transcriptional profile of zebrafish eyes after exposure to 350 mg/L Propylthiouracyl (PTU)

Project description:Vertebrate eye devlopment is partially regulated by thyroid hormones. Propylthiouracyl is a pharmaceutical that lowers thyroid hormone levels. We investigated the effects of PTU on eye development of zebrafish. We expected PTU exposure to cause transcriptional changes of visual-system-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Additionally, the reversibility of effects after recovery in clean water for three days was investigated.

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Single-cell RNA sequencing of zebrafish thyroid cells

Project description:The thyroid gland is responsible for supplying the thyroid hormones to the body. The gland is an endocrine organ with an intricate structure enabling production, storage and release of the thyroid hormones. The gland is composed of numerous spherical follicles of varying sizes, surrounded by thyroid follicular epithelial cells, or thyrocytes. The thyrocytes surrounding the follicles generate the thyroid hormones in a multi-step process. Though the machinery responsible for the production of thyroid hormones by thyrocytes is well established, it remains unknown if all the thyrocytes resident in the thyroid gland are equally capable of generating thyroid hormones. In other words, the extent of molecular homogeneity between individual thyrocytes has not yet been investigated. To obtain an unbiased picture into the molecular heterogeneity present in zebrafish thyrocytes, we performed droplet based next-generation sequencing of individual thyrod gland cells. Using unsupervised clustering, we could identify all the major cell types present in the thyroid gland. Moreover, we could define sub-populations within the major cell-types, demonstrating the presence of molecular heterogeneity within nominally homogenous cell-populations.

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Transcriptional profile of zebrafish eyes after exposure to 200 ug/L Tetrabromobisphenol A (TBBPA)

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