Embryotoxicity analysis of anti-arrhythmia drugs amiodarone, dronedarone, and their metabolites using 3D gastruloid models.

ABSTRACT: Amiodarone and dronedarone are anti-arrhythmic drugs that are structurally related but differ in iodine content. Although contraindicated during pregnancy due to suspected embryotoxicity based on animal studies, their mechanisms of action and relevance to human development remain unclear. Here, we used gastruloids - 3D aggregates of mouse or human pluripotent stem cells that recapitulate axial elongation morphogenesis of early embryos - to investigate their developmental effects. In mouse gastruloids, both drugs and their major metabolites impaired growth and elongation at 1.5 - 3.0 µM. They also altered expression of genes involved in somite segmentation and retinoic acid biosynthesis. Notably, dronedarone down-regulated additional genes, and only amiodarone's morphological effects were a

SUBMITTER: Kurashima CK 

PROVIDER: S-EPMC12662635 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature