Paper Details
- Masahiro Hosonuma (Pharmacological Research Center, Showa University / Department of Pharmacology, Showa University Graduate School of Medicine / masa-hero@med.showa-u.ac.jp)
- Masahiro Akiyama (Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University / Faculty of Medicine, University of Tsukuba / akiyama.sw@med.showa-u.ac.jp)
1) Graduate School of Media and Governance, Keio University , 2) Institute for Advanced Biosciences, Keio University , 3) Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University , 4) Department of Physiology, Showa University Graduate School of Pharmacy , 5) Department of Toxicology, Showa University Graduate School of Pharmacy , 6) Pharmacological Research Center, Showa University , 7) Department of Pharmacology, Showa University Graduate School of Medicine , 8) Department of Microbiology, School of Pharmacy, Kitasato University , 9) Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University , 10) Faculty of Medicine, University of Tsukuba , 11) Graduate School of Pharmaceutical Sciences, Kyusyu University
Methylmercury (MeHg), a potent neurotoxin, poses substantial risks to prenatal brain development by crossing the placental barrier. In our daily lives, we are exposed to various environmental metals simultaneously with MeHg. Therefore, the combined exposure effects of these metals and MeHg should be investigated. Hence, this study examined the combined fetal exposure effects of MeHg and copper (Cu), an essential element. Gene expression changes in the fetal brains of mice exposed to MeHg, Cu, or both were examined through RNA-seq analysis. Our results showed that the number of variable genes exposed to combined MeHg and Cu increased compared with that in single exposure. Most of them were gene variations specific to combined exposure. Gene Ontology biological process analysis revealed the amplified effects on GABAergic interneurons in the cerebral cortex under combined exposure. IPA pathway analysis indicated considerable variations in pathways related to oxidative stress, neuronal development, and energy metabolism, including the activation of NRF2-mediated oxidative stress response and the suppression of mitochondrial fatty acid beta-oxidation. These findings highlighted the complexity and enhanced risks of combined MeHg and Cu exposure. Therefore, neurodevelopmental effects were more severe and multifaceted than those caused by individual exposures. This research highlighted the importance of understanding the mechanisms of the combined exposure effects of MeHg.