Transcriptomic and Long-Term Behavioral Deficits Associated with Developmental 3.5 GHz Radiofrequency Radiation Exposures in Zebrafish

[Image: see text] The rapid deployment of the fifth-generation (5G) spectrum by the telecommunication industry is intended to promote better connectivity and data integration among various industries. However, concerns among the public about the safety and health effects of radiofrequency radiations (RFRs) emitted from the newer-generation cell phone frequencies remain, partly due to the lack of robust scientific data. Previously, we used developmental zebrafish to model the bioactivity of 3.5 GHz RFR, a frequency used by 5G-enabled cell phones, in a novel RFR exposure chamber. With RFR exposures from 6 h post-fertilization (hpf) to 48 hpf, we observed that, despite no teratogenic effects, embryos showed subtle hypoactivity in a startle response behavior assay, suggesting abnormal sensorimotor behavior. This study builds upon the previous one by investigating the transcriptomic basis of RFR-associated behavior effects and their persistence into adulthood. Using mRNA sequencing, we found a modest transcriptomic disruption at 48 hpf, with 28 differentially expressed genes. KEGG pathway analysis showed that biochemical pathways related to metabolism were significantly perturbed. Embryos were grown to adulthood, and then a battery of behavioral assays suggested subtle but significant abnormal responses in RFR-exposed fish across the different assays evaluated that suggest potential long-term behavioral effects. Overall, our study suggests the impacts of RFRs on the developing brain, behavior, and the metabolome should be further explored.