Bisphenol A and several derivatives exert neural toxicity in human neuron-like cells by decreasing neurite length. (January 2020)

• Record Type: Journal Article
• Authors: Liang, Xiaoxing; Yin, Nuoya; Liang, Shengxian; Yang, Renjun; Liu, Shuyu; Lu, Yuanping; Jiang, Linshu; Zhou, Qunfang; Jiang, Guibin; Faiola, Francesco
• Is Part Of: Food and chemical toxicology. Volume 135(2020)
• Publication Date: 2020-01
• Subjects: Bisphenol A (BPA) derivatives -- Human neural stem cells -- Human embryonic stem cells -- Neural toxicity -- Neurite length; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.111015
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Bisphenol A (BPA) and its derivatives, including bisphenols S (BPS), F (BPF), E (BPE), B (BPB), Z (BPZ), and AF (BPAF), are widely used in consumer products. Moreover, they are typically detected in the environment, food, and humans. Previous studies have linked BPA to several health risks, but it is still unclear whether BPA replacements are safe. In this study, we developed an in vitro model based on human embryonic stem cells (hESCs) to explore the potential neural toxicity of these compounds. We observed that the bisphenols affected the viability of hESCs and hESC-derived neural stem cells (NSCs) at high concentrations, with BPS being the least cytotoxic and BPAF the strongest cytotoxic compound. At human-relevant concentrations, the bisphenols did not significantly interfere with gene expression and protein levels during hESC differentiation into the neural epithelium, as well as during specification of neuron-like cells from NSCs. Nevertheless, monitoring of cell morphology changes indicated that exposure to BPA and its derivatives impaired neurite length in neuron-like cells. Thus, our findings provide insights into the molecular mechanisms of bisphenol-dependent neurotoxicity at low nanomolar levels and support the view that BPA substitutes may not be sufficiently safe for widespread use as industrial chemicals. Graphical abstract: Image 1 Highlights: BPA and its derivatives are cytotoxic at micromolar concentrations in hESCs and NSCs. Nanomolar concentrations of bisphenols decrease neurite length in neuron-like cells. BPA replacements may not be as safe as initially proposed.