Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice.

Bisphenol A (BPA), a widely used raw component of polycarbonate plastics and epoxy resins, has been reported to induce developmental neurotoxicity in offspring born to dams exposed to low doses of BPA; however, the toxicity mechanism remains elusive. To study the effects of in utero BPA exposure on neuronal morphology, we studied spine density and dendritic growth in the hippocampal CA1 of aged mice and developing mice prenatally exposed to low doses of BPA. Pregnant mice were orally administered BPA at a low dose of 0, 40, or 400 µg/kg body weight/day on gestational days 8.5-17.5/18.5. Mouse progenies were euthanized at 3 weeks or 14 months, and their brains were analyzed for dendritic arborization of GFP-expressing neurons or spine densities of Golgi-stained neurons in the hippocampal CA1. Regardless of the dose, in utero BPA exposure reduced spine densities in the hippocampal CA1 of the 14-month-old mice. In the developing brain from the 3-week-old mice born to dams exposed to BPA at a dose of 400 µg/kg body weight/day, overall length and branching number of basal dendrites but not apical dendrites were decreased. In utero low doses of BPA exposure disrupts hippocampal CA1 neuronal morphology during development, and this disruption is believed to persist in adulthood.

Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling.

Increased prevalence of mental disorders cannot be solely attributed to genetic factors and is considered at least partly attributable to chemical exposure. Among various environmental chemicals, in utero and lactational dioxin exposure has been extensively studied and is known to induce higher brain function abnormalities in both humans and laboratory animals. However, how the perinatal dioxin exposure affects neuromorphological alterations has remained largely unknown. Therefore, in this study, we initially studied whether and how the over-expression of aryl hydrocarbon receptor (AhR), a dioxin receptor, would affect the dendritic growth in the hippocampus of the developing brain. Transfecting a constitutively active AhR plasmid into the hippocampus via in utero electroporation on gestational day (GD) 14 induced abnormal dendritic branch growth. Further, we observed that 14-day-old mice born to dams administered with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dose: 0, 0.6, or 3.0 µg/kg) on GD 12.5 exhibited disrupted dendritic branch growth in both the hippocampus and amygdala. Finally, we observed that 16-month-old mice born to dams exposed to perinatal TCDD as described above exhibited significantly reduced spine densities. These results indicated that abnormal micromorphology observed in the developing brain may persist until adulthood and may induce abnormal higher brain function later in life.