Institute of Environmental Assessment and Water Research, IDAEA-CSIC, Barcelona, Catalunya, 08034, Spain; Universitat de Barcelona (UB), Barcelona, Catalunya, 08007, Spain.
Institute of Environmental Assessment and Water Research, IDAEA-CSIC, Barcelona, Catalunya, 08034, Spain.
Chemosphere. 2020 May;246:125704. doi: 10.1016/j.chemosphere.2019.125704. Epub 2019 Dec 20.
Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) has been shown to act as an obesogen and to disrupt lipid metabolism in zebrafish eleutheroembryos (ZE). To characterize the consequences of this disruption, we performed a detailed lipidomic study using ZE exposed to different BPA concentrations (0, 4, 6 and 8 mg/L of BPA) from day 2 to up to day 6 post fertilization (dpf). Total lipids at 4, 5 and 6 dpf were extracted by Folch method and analyzed by high-performance thin layer chromatography (HPTLC) as wide-range preliminary screening. Selected conditions (0 and 6 mg/L of BPA) were used to obtain a high-quality lipid profile using ultra high-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC-TOFMS). BPA exposed ZE exhibited increased amounts of triglycerides (TG), diglycerides (DG), phosphatidylcholines (PC) and phosphatidylinositols (PI), regarding the control group. Analysis of time- and BPA exposure-related patterns of specific lipid species showed a clear influence of unsaturation degree (mostly in DG and PC) and/or fatty acid chain length (mostly in TG and PC derivatives) on their response to the presence of BPA. A decreased yolk-sac and energy consumption in exposed individuals appeared as the main reason for the observed BPA-driven effects. Integration of these results with previous morphological, biochemical, transcriptomic, metabolomic and behavioral data suggests a disruption of different signalling pathways by BPA that starts at very low BPA concentrations, whose effects propagate across different organization levels, and that cannot be only explained by the relatively weak estrogenic effect of BPA.
双酚 A（BPA；4,4'-(丙烷-2,2-二基)二苯酚）已被证明具有致肥胖作用，并能破坏斑马鱼幼鱼（ZE）的脂质代谢。为了描述这种破坏的后果，我们使用暴露于不同浓度 BPA（0、4、6 和 8 mg/L BPA）的 ZE 进行了详细的脂质组学研究，从受精后第 2 天到第 6 天（dpf）。通过 Folch 法提取 4、5 和 6 dpf 的总脂质，并通过高效薄层色谱法（HPTLC）进行分析作为广泛的初步筛选。选择条件（0 和 6 mg/L BPA）用于使用超高效液相色谱/飞行时间质谱法（UHPLC-TOFMS）获得高质量的脂质谱。与对照组相比，暴露于 BPA 的 ZE 表现出甘油三酯（TG）、二甘油酯（DG）、磷脂酰胆碱（PC）和磷脂酰肌醇（PI）的含量增加。分析特定脂质种类的时间和 BPA 暴露相关模式表明，不饱和程度（主要在 DG 和 PC 中）和/或脂肪酸链长（主要在 TG 和 PC 衍生物中）对它们对 BPA 存在的反应有明显影响。暴露个体卵黄囊和能量消耗的减少似乎是观察到的 BPA 驱动效应的主要原因。将这些结果与先前的形态学、生物化学、转录组学、代谢组学和行为数据相结合表明，BPA 开始于非常低的 BPA 浓度，通过破坏不同的信号通路，其影响会在不同的组织水平上传播，并且不能仅用 BPA 相对较弱的雌激素效应来解释。
