Evaluation and mechanistic study of chlordecone-induced thyroid disruption: Based on in vivo, in vitro and in silico assays.

The present study aimed to evaluate the thyroid-disrupting potency of chlordecone, and reveal the underlying mechanism. In the in vivo assays, rare minnow embryos were exposed to 0, 0.01, 0.1, 1 and 10 μg·L-1 chlordecone until sexually mature. The results showed decreased T4 but increased T3 concentrations in plasma, upregulated mRNA levels of thyrotropin-releasing hormone receptor (trhr) and sodium-iodide symporter (nis) in the brain, and transthyretin (ttr), thyroid hormone receptor α (trα) and deiodinase enzymes (dio1 and dio2) in the liver of adult fish. In the in vitro assays, single chlordecone treatments promoted growth hormone (GH) and prolactin (PRL) secretion in GH3 cells. Transcription of thyroid receptor (trβ) was inhibited, but this is not likely responsible for chlordecone-induced GH secretion and altered transcription. When co-treated with T3, chlordecone acted independently of the effect of T3 on GH secretion; chlordecone-induced GH/PRL secretion and mRNA expression were further promoted when co-treated with E2, but inhibited when co-treated with ICI, indicating an important role for estrogen receptors (ERs) in chlordecone-induced changes in GH3 cells. Furthermore, in silico prediction suggested no stable interactions between chlordecone and thyroid hormone-related proteins, as well as a regulatory role for ERs in thyroid systems. Overall, our results indicated that chlordecone may have adverse effects on thyroid systems upon long-term exposure. However, rather of TRs, ERs may be responsible for thyroid disruption following chlordecone exposure.