High Salt Exposure Disrupts Cardiovascular Development in Zebrafish Embryos, Brachyodanio rerio, via Calcium and MAPK Signaling Pathways

Cardiovascular disease and hypertension are leading global health concerns. Modern fast-paced lifestyles have contributed to increased dietary salt intake, which affects not only adults but also fetal development. However, the impact of high salt exposure on embryogenesis remains underexplored. Danio rerio (zebrafish) embryos offer a powerful model for studying vertebrate development due to their transparency, rapid growth, and physiological similarity to humans. In this study, we examined the morphological and genetic effects of high salt exposure using a 2% NaCl environment to simulate conditions relevant to maternal high salt intake during pregnancy. Fertilized zebrafish embryos were exposed to either standard media (control) or 2% salt from 3 hours post-fertilization (hpf) to 96 hpf. Morphological development was documented through microscopy, and hatch and heart rates were assessed at multiple time points. RNA sequencing (RNA-Seq) was performed to identify gene expression changes associated with salt exposure. High salt treatment delayed embryonic development, with hatch rates lagging approximately 24 hours behind controls. Heart rate was significantly reduced in the salt group on days 2 and 3. Transcriptomic analysis revealed substantial changes in gene expression, with 2,133 genes upregulated and 2,190 downregulated in the salt-treated group. Pathway enrichment analysis identified disruptions in calcium signaling, MAPK signaling, cardiac muscle development, and vascular smooth muscle contraction. These findings suggest that high salt exposure during early development alters critical signaling pathways and physiological processes, providing mechanistic insights that may inform our understanding of cardiovascular risk programming during fetal development.