Medium-Chain Chlorinated Paraffins Trigger Thyroid Hormone Synthesis and Interfere with Mitochondrial Function in the...

Area of Science:

• Environmental toxicology
• Endocrinology
• Molecular biology

Background:

• Medium-chain chlorinated paraffins (MCCPs) are widespread environmental contaminants.
• Concerns exist regarding MCCP toxicity, with proposed listing under the Stockholm Convention.
• The precise toxicological mechanisms of MCCPs remain largely uncharacterized.

Purpose of the Study:

• To investigate the toxic effects of MCCPs on the thyroid gland in female Sprague-Dawley rats.
• To elucidate the molecular pathways underlying MCCP-induced thyroid toxicity using transcriptomics and metabolomics.
• To provide insights for mechanism-based risk assessment of MCCPs.

Main Methods:

• Administration of MCCPs (0.1-50 mg/kg body weight/day) to rats.
• Histopathological examination of thyroid follicular cells.
• Measurement of serum thyroid hormones and related regulatory factors.
• Transcriptomic and metabolomic analyses to identify affected pathways.

Main Results:

• MCCP exposure induced histopathological changes in thyroid follicular cells, including endoplasmic reticulum and mitochondrial alterations.
• Elevated serum levels of thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroxine were observed at higher doses.
• Transcriptomic analysis revealed upregulation of genes involved in thyroid hormone synthesis.
• Integrated omics data indicated mitochondrial dysfunction mediated by alterations in fatty acid oxidation, the Krebs cycle, and oxidative phosphorylation.

Conclusions:

• MCCPs exhibit toxicity to the thyroid gland by stimulating thyroid hormone synthesis and disrupting mitochondrial function.
• The observed metabolic toxicity is potentially linked to the chlorine content of MCCPs.
• This research offers novel insights into the modes of action and mechanism-based risk assessment of MCCPs.