title: In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice.
abstract: Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA-40), or 400 (BPA-400) μg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner.
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo , Tokyo , Japan.
authors: Wenting
authors: W
authors: Ling
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo , Tokyo , Japan.
authors: Toshihiro
authors: T
authors: Endo
authors: Department of Anatomy, Keio University School of Medicine , Tokyo , Japan.
authors: Ken-Ichiro
authors: K
authors: Kubo
authors: Department of Anatomy, Keio University School of Medicine , Tokyo , Japan.
authors: Kazunori
authors: K
authors: Nakajima
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Laboratory for Systems Neuroscience and Preventive Medicine, Faculty of Human Sciences, Waseda University, Tokorozawa, Japan.
authors: Masaki
authors: M
authors: Kakeyama
authors: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Chiharu
authors: C
authors: Tohyama
keywords: bisphenol A; brain development; cerebral cortex; environmental chemicals; low dose; neuronal migration