The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line

Yuki Fujiwara,Takahiko Katoh,Noriyuki Koibuchi,Wataru Miyazaki

doi:10.3389/fendo.2018.00024

Yuki Fujiwara, Takahiko Katoh + Show 2 more

Open Access

https://doi.org/10.3389/fendo.2018.00024

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Abstract

Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

Highlights

A variety of environmental chemicals are known to induce adverse effects in animals and humans including general toxicity, carcinogenesis, mutagenesis, and reproductive toxicity
To examine whether bisphenol A (BPA) exposure induced ReNcell ventral mesencephalon (VM) cell death, we investigated the cytotoxicity of BPA using a Cell Counting Kit-8 (CCK-8) (DOJINDO LABORATORIES, Kumamoto, Kyushu, Japan)
We investigated the ratio of differentiated cell types using a real-time PCR method with various neural markers, such as βIII-tubulin for neurons during differentiation, microtubule-associated protein 2 (MAP2) for mature neuron, glial fibrillary acidic protein (GFAP) and S100β for astrocytes, Olig2 for oligodendrocytes, and nestin, Dcx, NCAM 1, and MCT 1 for neural stem/progenitor cells (NPCs)

Summary

Introduction

A variety of environmental chemicals are known to induce adverse effects in animals and humans including general toxicity (e.g., organ damage), carcinogenesis, mutagenesis, and reproductive toxicity. Several animal studies have shown that gestational exposure to low-dose toxicants, such as dioxin, may cause adverse effects including neurodevelopmental alterations without affecting. BPA Disrupts Neural Differentiation the dams [1, 2]. These reports suggested that the developing brain is vulnerable to exposure to environmental chemicals, even at low doses. Many studies have demonstrated neurodevelopmental and behavioral disorders attributable to gestational and/or lactational exposure to environmental chemicals. We have previously shown that during the maternal and postnatal periods, dioxin can cross the developing blood–brain barrier and cause learning deficits, emotional abnormalities, and changes in social behavior [3,4,5]

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