Thyroid Disruption Assays

Thyroid Disruption Assays

Environmental contaminants with endocrine disrupting properties (endocrine disrupting compounds, EDCs) affect humans and wildlife through interfering with endocrine homeostasis and hormonal processes, such as oestrogen and thyroid signaling. EDCs can modulate the endocrine system by multiple mechanisms of action and possibly cause birth defects, cancerous tumors, and other developmental disorders. An important endocrine system that is targeted by various environmental contaminants is the thyroid hormone system. Field surveys, epidemiological studies as well as laboratory experiments on birds, fish, amphibians or humans provide ample evidence that exposure to environmental pollutants can be associated with disruption of thyroid hormone synthesis, metabolism and/or transport and thus can result in altered thyroid hormone status and thyroid hormone signaling.

In vertebrates, thyroid hormones (THs) play vital roles in many physiological processes including growth, development, metabolism, energy balance, and reproduction action. Many studies have indicated that the toxicity profiles of mammalian and zebrafish are very similar. In zebrafish, the hypothalamic-pituitary-thyroid (HPT) axis controls the thyroid endocrine system which is responsible for regulating the synthesis of THs. Besides, the early life stages of zebrafish is the most vulnerable to environmental pollutants, and developing zebrafish embryos/larvae is considered to be a reliable model to evaluate thyroid endocrine disruption by chemical treatment.

Diagram of zebrafish thyroid development.

Figure 1. Diagram of zebrafish thyroid development.

Our Zebrafish Thyroid Disruption Assays

In vivo assays are the most appropriate methods to elucidate the potential effects of a toxicant on the thyroid system. Available assays with zebrafish embryos target TH levels either directly or indirectly through measuring the corresponding gene expression of enzymes involved in the TH synthesis. Creative Biogene has developed a bioassay to screen the thyroid disrupting potential of chemical compounds using tg(tg:mcherry) transgenic embryos, which express red fluorescence in the thyroid gland under the thyroglobulin promoter. Given the negative feedback mechanism that regulates TH synthesis, hyper- and hypothyroidism may be efficiently measured by differences of intensity in the tg:mCherry fluorescence. The fluorescence signal is related to the expression of genes involved in the TH synthesis.

Workflow

  • Zebrafish maintenance and exposure
  • Assessment of toxicity
  • Screening of tg(tg:mCherry) embryos
  • Image analysis
  • Gene expression analysis

Creative Biogene provides an efficient screening tool for the detection of compounds with thyroid disrupting activities. Contact us to learn more about our zebrafish thyroid disruption assay services.

References

  • Jarque S, et al. An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos. PloS one, 2018, 13(8).
  • Zhang D, et al. Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae. PLoS One, 2017, 12(5).
  • Tang T, et al. Thyroid disruption in zebrafish larvae by short-term exposure to bisphenol AF. International journal of environmental research and public health, 2015, 12(10): 13069-13084.
  • Baumann L, et al. Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions. Aquatic toxicology, 2016, 172: 44-55.
  • Marelli F, Persani L. How zebrafish research has helped in understanding thyroid diseases. F1000Research, 2017, 6.

For research use only. Not intended for any clinical use.

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