In utero bisphenol A exposure induces abnormal neuronal migration in the cerebral cortex of mice

Wenting Ling, Toshihiro Endo, Ken ichiro Kubo, Kazunori Nakajima, Masaki Kakeyama, Chiharu Tohyama

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    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.

    Original languageEnglish
    Article number7
    JournalFrontiers in Endocrinology
    Volume7
    Issue numberFEB
    DOIs
    Publication statusPublished - 2016

    Fingerprint

    Cerebral Cortex
    Electroporation
    bisphenol A
    Brain
    Laboratory Animals
    Genes
    Plasmids
    Neurons
    Control Groups

    Keywords

    • Bisphenol A
    • Brain development
    • Cerebral cortex
    • Environmental chemicals
    • Low dose
    • Neuronal migration

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism

    Cite this

    In utero bisphenol A exposure induces abnormal neuronal migration in the cerebral cortex of mice. / Ling, Wenting; Endo, Toshihiro; Kubo, Ken ichiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu.

    In: Frontiers in Endocrinology, Vol. 7, No. FEB, 7, 2016.

    Research output: Contribution to journalArticle

    Ling, Wenting ; Endo, Toshihiro ; Kubo, Ken ichiro ; Nakajima, Kazunori ; Kakeyama, Masaki ; Tohyama, Chiharu. / In utero bisphenol A exposure induces abnormal neuronal migration in the cerebral cortex of mice. In: Frontiers in Endocrinology. 2016 ; Vol. 7, No. FEB.
    @article{a23b8c65410443b88c9737b16f3efdae,
    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.",
    keywords = "Bisphenol A, Brain development, Cerebral cortex, Environmental chemicals, Low dose, Neuronal migration",
    author = "Wenting Ling and Toshihiro Endo and Kubo, {Ken ichiro} and Kazunori Nakajima and Masaki Kakeyama and Chiharu Tohyama",
    year = "2016",
    doi = "10.3389/fendo.2016.00007",
    language = "English",
    volume = "7",
    journal = "Frontiers in Endocrinology",
    issn = "1664-2392",
    publisher = "Frontiers Media S. A.",
    number = "FEB",

    }

    TY - JOUR

    T1 - In utero bisphenol A exposure induces abnormal neuronal migration in the cerebral cortex of mice

    AU - Ling, Wenting

    AU - Endo, Toshihiro

    AU - Kubo, Ken ichiro

    AU - Nakajima, Kazunori

    AU - Kakeyama, Masaki

    AU - Tohyama, Chiharu

    PY - 2016

    Y1 - 2016

    N2 - 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.

    AB - 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.

    KW - Bisphenol A

    KW - Brain development

    KW - Cerebral cortex

    KW - Environmental chemicals

    KW - Low dose

    KW - Neuronal migration

    UR - http://www.scopus.com/inward/record.url?scp=84962566134&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84962566134&partnerID=8YFLogxK

    U2 - 10.3389/fendo.2016.00007

    DO - 10.3389/fendo.2016.00007

    M3 - Article

    AN - SCOPUS:84962566134

    VL - 7

    JO - Frontiers in Endocrinology

    JF - Frontiers in Endocrinology

    SN - 1664-2392

    IS - FEB

    M1 - 7

    ER -