mRNA-miRNA sequencing reveals mechanisms of 2,2'-dipyridyl disulfide-induced thyroid disruption in Japanese flounder (Paralichthys olivaceus).

This study was conducted to evaluate the thyroid-disrupting effects of 2,2'-dipyridyl disulfide using Japanese flounder (Paralichthys olivaceus) as an animal model and to reveal the underlying mechanisms from the perspective of miRNA-mRNA interactions. The results indicated that 2,2'-dipyridyl disulfide exposure decelerated the metamorphic progress of P. olivaceus, suggesting its thyroid-disrupting property as an antagonist. Furthermore, radioimmunoassays, thyroid histological observation, real-time polymerase chain reaction, and mRNA sequencing showed that 2,2'-dipyridyl disulfide exposure exerted its thyroid-disrupting effects on larval and juvenile P. olivaceus by targeting multiple processes and pathways involved in the thyroid system, including peripheral metabolism of thyroid hormones, the thyroid hormone synthesis pathway, and the thyroid hormone/thyroid hormone receptor signaling pathway. In particular, global upregulation of the gene expression of three deiodinases caused decreases in thyroid hormone levels after 2,2'-dipyridyl disulfide exposure that are believed to be responsible for the inhibition of metamorphosis in P. olivaceus. Finally, miRNA sequencing suggested that several evolutionarily conserved miRNAs play important roles in the mechanism of 2,2'-dipyridyl disulfide-induced thyroid disruption. Specifically, overexpression of pny-miR-723a and pny-miR-216a resulted in upregulation of deiodinase 1 mRNA levels in the 2,2'-dipyridyl disulfide exposure group. This study provides the first evidence that 2,2'-dipyridyl disulfide has thyroid-disrupting properties and is also the first study remarking on the roles of miRNA-mRNA interactions in the action mechanisms of thyroid disruptors. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Hua Tian, Wanyu Ba, Xu Zhang, Xue Wang, Yifei Dong, Xuefu Li, Shaoguo Ru. mRNA-miRNA sequencing reveals mechanisms of 2,2'-dipyridyl disulfide-induced thyroid disruption in Japanese flounder (Paralichthys olivaceus). Aquatic toxicology (Amsterdam, Netherlands). 2022 Jul;248:106191

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PMID: 35576717

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