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

Area of Science:

• Developmental toxicology
• Ophthalmology
• Endocrinology

Background:

• Thyroid hormones are crucial for vertebrate development, including eye formation.
• Thyroid hormone disrupting chemicals (THDCs) pose risks to developmental processes.
• Previous studies indicated THDCs can cause eye malformations and dysfunction.

Purpose of the Study:

• To investigate the effects of THDCs on zebrafish eye development at the transcriptional level.
• To compare the impacts of a synthesis inhibitor (PTU) and a receptor antagonist (TBBPA).
• To assess the reversibility of THDC-induced changes in eye gene expression.

Main Methods:

• Zebrafish embryos (0-5 dpf) were exposed to PTU or TBBPA.
• Full genome microarray analysis of RNA from eye tissue.
• Assessment of gene expression changes and Gene Ontology (GO) terms.
• Investigation of effects after a 3-day recovery period.

Main Results:

• Both PTU and TBBPA altered transcripts related to phototransduction.
• PTU caused widespread down-regulation (>90%) in "sensory perception" genes, while TBBPA caused up-regulation (>80%).
• Transcriptional alterations persisted 3 days post-exposure, with no full recovery observed.

Conclusions:

• THDCs significantly impact eye development by altering vision-related gene expression.
• Different THDCs elicit distinct transcriptional responses in the developing zebrafish eye.
• While some recovery mechanisms are activated, THDC exposure leads to persistent transcriptional changes in eye tissues.