Comparative thyroid disruption by o,p'-DDT and p,p'-DDE in zebrafish embryos/larvae

Area of Science:

• Environmental Toxicology
• Endocrinology
• Developmental Biology

Background:

• Thyroid disruption by organochlorine pesticides like o,p -DDT and p,p -DDE is known.
• The precise molecular mechanisms underlying these thyroid disturbances in aquatic organisms, specifically fish, remain poorly understood.
• Investigating these mechanisms is crucial for assessing the ecological risks of these persistent pollutants.

Purpose of the Study:

• To elucidate the mechanisms of thyroid dysfunction induced by o,p -DDT and p,p -DDE in zebrafish larvae.
• To analyze alterations in thyroid hormone levels and gene expression within the hypothalamic-pituitary-thyroid (HPT) axis.
• To evaluate the developmental toxicity associated with exposure to these DDT isomers.

Main Methods:

• Zebrafish embryos and larvae were exposed to varying concentrations of o,p -DDT and p,p -DDE for seven days.
• Thyroid hormone levels (T4, T3) and gene expression related to the HPT axis and thyroid development were quantified.
• Developmental endpoints including survival, body length, and malformation rates were assessed.

Main Results:

• Both o,p -DDT and p,p -DDE exposure led to the up-regulation of genes involved in thyroid hormone synthesis and development.
• o,p -DDT exposure increased whole-body T4 and T3 levels, with down-regulation of ugt1ab and dio3.
• p,p -DDE exposure decreased whole-body T4 and T3 levels, associated with altered expression of dio2 and ugt1ab, and impaired T3/T4 ratio, alongside developmental defects.

Conclusions:

• o,p -DDT and p,p -DDE induce distinct molecular responses in the zebrafish HPT axis, leading to thyroid disruption.
• The study highlights differential impacts on thyroid hormone homeostasis and gene regulation between the two compounds.
• Both chemicals pose developmental risks to zebrafish larvae, underscoring their potential as endocrine-disrupting chemicals in aquatic ecosystems.