Bisphenol A exposure induces increased microglia and microglial related factors in the murine embryonic dorsal telencephalon and hypothalamus

Mifumi Takahashi; Munekazu Komada; Ken Miyazawa; Shigemi Goto; Yayoi Ikeda

doi:10.1016/j.toxlet.2017.12.010

Bisphenol A exposure induces increased microglia and microglial related factors in the murine embryonic dorsal telencephalon and hypothalamus

Toxicol Lett. 2018 Mar 1:284:113-119. doi: 10.1016/j.toxlet.2017.12.010. Epub 2017 Dec 14.

Authors

Mifumi Takahashi¹, Munekazu Komada², Ken Miyazawa³, Shigemi Goto³, Yayoi Ikeda⁴

Affiliations

¹ Department of Anatomy, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
² Department of Anatomy, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan. Electronic address: komada@dpc.agu.ac.jp.
³ Department of Orthodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
⁴ Department of Anatomy, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan. Electronic address: yayoi@dpc.agu.ac.jp.

PMID: 29248573
DOI: 10.1016/j.toxlet.2017.12.010

Abstract

Bisphenol A (BPA) is a widely used compound in the food packaging industry. Prenatal exposure to BPA induces histological abnormalities in the neocortex and hypothalamus in association with abnormal behaviors. Yet, the molecular and cellular neurodevelopmental toxicological mechanisms of BPA are incompletely characterized on neuroinflammatory-related endopoints. To evaluate the neurodevelopmental effects of BPA exposure in mouse embryos, we examined microglial numbers as well as the expression of microglial-related factors in the E15.5 embryonic brain. BPA-exposed embryos exhibited significant increases in Iba1-immunoreactive microglial numbers in the dorsal telencephalon and the hypothalamus compared to control embryos. Further, the expression levels of microglial markers (Iba1, CD16, iNOS, and CD206), inflammatory factors (TNFα and IL4), signal transducing molecules (Cx3Cr1 and Cx3Cl1), and neurotrophic factor (IGF1) were altered in BPA-exposed embryos. These findings suggest that BPA exposure increases microglial numbers in the brain and alters the neuroinflammatory status at a transcriptional level. Together, these changes may represent a novel target for neurodevelopmental toxicity assessment after BPA exposure.

Keywords: Bisphenol A; Dorsal telencephalon; Hypothalamus; Microglia; Neuroinflammation.

MeSH terms

Animals
Behavior, Animal / drug effects
Benzhydryl Compounds / toxicity*
Biomarkers / analysis
Cell Count
Dose-Response Relationship, Drug
Environmental Pollutants / toxicity*
Female
Food Packaging
Gene Expression / drug effects
Hypothalamus / drug effects*
Hypothalamus / embryology
Inflammation Mediators / immunology
Male
Mice, Inbred ICR
Microglia / drug effects*
Microglia / immunology
Microglia / metabolism
Microglia / pathology
Neurogenesis / drug effects
Phenols / toxicity*
Pregnancy
Prenatal Exposure Delayed Effects / chemically induced*
Prenatal Exposure Delayed Effects / immunology
Prenatal Exposure Delayed Effects / metabolism
Prenatal Exposure Delayed Effects / pathology
Telencephalon / drug effects*
Telencephalon / embryology

Substances

Benzhydryl Compounds
Biomarkers
Environmental Pollutants
Inflammation Mediators
Phenols
bisphenol A