Zebrafish as a Model Organism in Space Biology Research

As deep-space exploration advances, the health effects of the space environment have become a critical concern. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model for space biology owing to their genetic tractability, optical transparency, and conserved organ systems. This review summarizes recent advances in using zebrafish to study spaceflight-associated health risks, focusing on ionizing radiation and altered gravity. We examine effects across the cardiovascular, nervous, musculoskeletal, sensory, reproductive, and other systems. Radiation induces cardiac dysfunction, neurobehavioral deficits, skeletal deformation, ocular damage, and reproductive toxicity, often through oxidative stress, apoptosis, and dysregulated signaling pathways. Microgravity and hypergravity primarily affect the musculoskeletal and vestibular systems, with microgravity reducing bone ossification and impairing otolith development. We also discuss current limitations, including the gap between ground-based simulations and actual space conditions, and the lack of combined-stressor studies. Finally, we highlight future directions, such as in-orbit live imaging, CRISPR/Cas9-based validation, and high-throughput countermeasure screening. This review aims to provide a theoretical framework for using zebrafish to assess space-environment-associated health risks and to inform research on health risks relevant to long-duration spaceflight.