AUTHOR=Miao Xia , Lin Yanyun , Guo Juan , Lin Jiajin , Gao Peng , Zhang Wei , Zeng Lihua , Guo Guozhen , Li Jing TITLE=Differential metabolic responses of mouse Leydig and spermatogonia cells to radiofrequency electromagnetic field exposure JOURNAL=Frontiers in Public Health VOLUME=Volume 13 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1623701 DOI=10.3389/fpubh.2025.1623701 ISSN=2296-2565 ABSTRACT=IntroductionAlthough existing studies have shown that radiofrequency electromagnetic fields (RF-EMFs) have a variety of effects on living organisms, the specific impact of RF-EMFs on the metabolism of reproductive cells and their underlying mechanisms remain unclear.This study aims to explore the effects of RF-EMFs on the metabolism of mouse Leydig cells (TM3) and spermatogonia cells (GC-1) through metabolomics analysis, revealing the potential mechanisms by which RF-EMFs affect reproductive health.MethodsWe employed liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolomic profiles of TM3 and GC-1 cells under two irradiation modalities: continuous and intermittent RF-EMF exposure. The data were further analyzed using KEGG pathway analysis to identify significantly enriched metabolic pathways. The ELISA (Enzyme-Linked Immunosorbent Assay) was used to detect glutathione levels.ResultsOur results showed that continuous irradiation had a more pronounced impact on the metabolism of TM3 cells, primarily affecting amino acid metabolism, the citric acid cycle, ABC transporters, bile secretion, and glutathione metabolism. In contrast, intermittent irradiation mainly altered the levels of fatty acyls and purine nucleosides, with significant enrichment in purine metabolism, biosynthesis of unsaturated fatty acids, and fatty acid metabolism. Compared to TM3 cells, GC-1 cells exhibited lower sensitivity to RF-EMF irradiation. Both irradiation modalities affected purine metabolism and lysine degradation pathways in TM3 cells, suggesting that changes in ADP levels may serve as a key metabolic signature in the cellular response to RF-EMF exposure.ConclusionContinuous irradiation significantly impacts TM3 cell metabolism, particularly amino acid and glutathione pathways, while intermittent irradiation mainly affects fatty acyls and purine metabolism. GC-1 cells show lower sensitivity to RF-EMF. ADP level changes may be a key metabolic signature of RF-EMF exposure.