title: Prenatal exposure to di(2-ethylhexyl) phthalate impairs development of the mouse neocortex.
abstract: Di(2-ethylhexyl) phthalate (DEHP) is currently the most commonly used phthalate for the production of flexible polyvinyl chloride. Phthalates including DEHP have been labeled as potential endocrine disruptors. The effect on the development of the neocortex, however, is unknown. To evaluate the neurodevelopmental effects of prenatal DEHP exposure at 1 and 100mg/kg/day or 100 and 500mg/kg/day in fetal and newborn mice, we performed a detailed histologic analysis of the developing dorsal telencephalon and neocortex. The observation of fetuses exposed to DEHP revealed reductions of proliferation and neurogenesis (1 and 100mg/kg) and an increase in cell death (500mg/kg). In addition, the newborns prenatally exposed to DEHP showed an abnormal neuronal distribution and a decrease in neurons. These findings suggest that prenatal DEHP exposure induces neurodevelopmental toxicity associated with the neural stem cell niche and corticogenesis.
authors.affiliation: 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.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Komada
authors.affiliation: Department of Life Science, Kindai University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan. Electronic address: yuuya-gendai@me.pikara.ne.jp.
authors.forename: Yuuya
authors.initials: Y
authors.lastname: Gendai
authors.affiliation: Department of Life Science, Kindai University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan. Electronic address: kagawa@life.kindai.ac.jp.
authors.forename: Nao
authors.initials: N
authors.lastname: Kagawa
authors.affiliation: Department of Life Science, Kindai University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan. Electronic address: tnagao@life.kindai.ac.jp.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nagao
mesh_terms: D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019579:Neocortex / Q000187:drug effects* / Q000254:growth & development*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D052244:Endocrine Disruptors; D004051:Diethylhexyl Phthalate
keywords: DEHP; Dorsal telencephalon; Neocortex; Neurogenesis; Neuronal distribution; Proliferation