Niclosamide Induces Epiboly Delay During Early Zebrafish Embryogenesis

Area of Science:

• Developmental toxicology
• Drug repurposing
• Zebrafish model

Background:

• Niclosamide is an antihelminthic drug with potential applications in cancer, bacterial infections, and Zika virus treatment.
• New therapeutic uses may involve non-oral delivery, raising concerns about in utero exposure and embryonic toxicity.

Purpose of the Study:

• To investigate the mechanism of niclosamide toxicity during early embryonic development.
• To determine if niclosamide affects embryonic development via oxidative phosphorylation or microtubule disruption.

Main Methods:

• Zebrafish embryos were exposed to varying concentrations of niclosamide during the maternal-to-zygotic transition.
• Epiboly progression, embryonic oxygen consumption, and mRNA expression were analyzed.
• In vitro tubulin polymerization assays were performed.

Main Results:

• Niclosamide caused a concentration-dependent delay in epiboly progression during late blastula and early gastrula stages.
• This delay was dependent on exposure during the maternal-to-zygotic transition.
• Niclosamide did not affect embryonic oxygen consumption but significantly impacted zygotic genome activation and cytoskeleton/cell cycle gene expression.
• Niclosamide inhibited tubulin polymerization in vitro.

Conclusions:

• Niclosamide-induced epiboly delay in zebrafish is likely due to disruption of microtubule formation and cell motility.
• The mechanism of toxicity does not appear to involve oxidative phosphorylation.
• Findings highlight potential developmental risks associated with niclosamide exposure during early embryogenesis.