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.

Mechanistic revealing of reproductive behavior impairment in male guppy (Poecilia reticulata) induced by environmentally realistic 2,2'-dithiobis-pyridine exposure.

Although (PS)2, the primary degradation product of emerging antifouling biocides metal pyrithiones (MePTs), can disrupt the reproductive behavior of fish at an environmentally relevant ng/L level, the underlying mechanism is still largely unknown. This study exposed sexually mature male guppy (Poecilia reticulata) to 20, 200, and 2000 ng/L (PS)2 to explore the compromised effect of (PS)2 on reproductive behavior through a realistic competing scenario. The results showed that (PS)2 suppressed male guppies' sexual interest to stimulus females, reduced their competitive behavior frequencies toward rival males, and decreased their mating time and frequency. (PS)2 exposure did not affect male guppies' secondary sexual characteristics or induce estrogenic activity. Whole-brain transcriptome sequencing identified 1070 differentially expressed genes (DEGs) with 872 up-regulated genes, which were functionally enriched into Gene Ontology terms pertaining to extracellular matrix (ECM) and extracellular region. KEGG enrichment for the DEGs uncovered that the activations of ECM-receptor interaction and focal adhesion pathways could be the underlying molecular mechanism implicated in the (PS)2 induced reproductive behavior impairment. This work would deliver a substantial contribution to the understanding of the ecological safety of MePTs biocides.