Are 5G radiofrequency electromagnetic fields and PARP1 interfering in the development of human iPSC-derived...

The rapid expansion of wireless technologies has increased exposure to radiofrequency electromagnetic fields (RF-EMF), with evolving frequencies and network configurations complicating assessment of potential health risks. Although no conclusive evidence links RF-EMF exposure to adverse health outcomes, including neurodevelopmental disorders or neurodegeneration, some studies suggest possible effects on cognitive functions. In this study, we address the role of poly(ADP-ribose) polymerase 1 (PARP1), a protein involved in neuronal development and neurodegeneration, and evaluate potential effects of RF-EMF. Dopaminergic neurons derived from wild-type (WT) and PARP1-knockout (KO) human induced pluripotent stem cells (hiPSCs) were exposed to RF-EMF during differentiation. PARP1 levels in WT cells decreased between differentiation and maturation, supporting its role during early neuronal development. The absence of PARP1 resulted in a prominent increase in dopaminergic phenotype at maturation when compared to differentiation, while protein levels of the dopaminergic progenitor marker decreased. Neuronal maturity was unaffected by genotype, while increased expression of the presynaptic marker synaptophysin suggests enhanced synaptic function in PARP1-KO cells compared to WT cells. Neuronal activity was developing over time in both WT and PARP1-KO cells. However, PARP1 deficiency was associated with selective changes in spike timing and burst-related properties, particularly at early and late differentiation stages. RF-EMF exposure did not alter the neuronal phenotype, development, synaptic integrity, or electrical activity in either genotype. Proteomic analysis further supports that genotype-dependent differences were greater than any RF-EMF-related exposure effects. Future studies should assess RF-EMF exposure at later developmental stages and investigate PARP1 function in disease-relevant models. In conclusion, PARP1 absence was associated with an enhanced dopaminergic phenotype, indicating that PARP1 may influence neuronal differentiation, maturation, and synaptic plasticity. Electrical activity increased with maturation time, consistent with progressive functional development of the neuronal culture. Overall, neuronal development was predominantly influenced by the genotype, whereas RF-EMF exposure produced only transient effects on the dopaminergic phenotype. Evidence of a genotype-dependent response to RF-EMF exposure was observed only for SYP and mTOR.