Gonadotropin releasing hormone (GnRH) neurons in the brain are the main controllers of reproduction and reproductive behavior in most vertebrates, and are susceptible to endocrine disruption by different bisphenols. While the endocrine disrupting properties of bisphenol A have been well documented, commonly used analogues such as bisphenol F (BPF) are not as well studied. In this study we examined the effects of early, low-dose, chronic BPF exposure on the development of the GnRH neural system in the zebrafish embryo. Using a transgenic zebrafish model system with GnRH3 neurons tagged with green fluorescent protein (GFP), developing GnRH neurons in both the terminal nerve (TN) and preoptic area (POA) were observed. These are neuronal populations with the former associated with allied reproductive behaviors and the latter associated with pituitary-gonadal axis control. Embryos were exposed in vitro to 0.25, 0.5 and 1 μM BPF from fertilization to 3 days post fertilization (dpf). At 0.25 μM BPF exposure, both POA- and TN- GnRH3 neurons showed significant reductions in neural area at 2 dpf that did not persist to 3 dpf. The higher BPF doses did not show neuron size differences at 2 dpf, but showed reduction in TN-GnRH3 neuron area at 3 dpf. These effects of BPF were closely mimicked by different doses of estradiol. An estrogen antagonist, ICI, mitigated BPF effects on the embryo. This is the first study to show that BPF affects the developing GnRH neural system via an estrogen-mediated pathway.

中文翻译：

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双酚F通过雌激素机制引起斑马鱼促性腺激素释放激素神经发育的破坏。

大脑中的促性腺激素释放激素（GnRH）神经元是大多数脊椎动物繁殖和生殖行为的主要控制者，并且易受不同双酚的内分泌干扰。尽管双酚A的内分泌干扰特性已得到充分证明，但对常用的类似物如双酚F（BPF）的研究也不够深入。在这项研究中，我们检查了早期，低剂量，长期BPF暴露对斑马鱼胚胎中GnRH神经系统发育的影响。使用带有标记有绿色荧光蛋白（GFP）的GnRH3神经元的转基因斑马鱼模型系统，观察到了末梢神经（TN）和视前区（POA）中正在发育的GnRH神经元。这些是神经元种群，前者与相关的生殖行为有关，而后者与垂体-性腺轴控制有关。从受精到受精后3天（dpf），将胚胎在体外暴露于0.25、0.5和1μMBPF中。在0.25μMBPF暴露下，POA-和TN- GnRH3神经元在2 dpf时神经区域均显示出明显减少，但并没有持续至3 dpf。较高的BPF剂量在2 dpf时未显示神经元大小差异，但在3 dpf时显示TN-GnRH3神经元面积减少。不同剂量的雌二醇密切模仿了BPF的这些作用。雌激素拮抗剂ICI减轻了BPF对胚胎的影响。这是第一项表明BPF通过雌激素介导的途径影响发育中的GnRH神经系统的研究。受精至受精后3天（dpf）为5和1μMBPF。在0.25μMBPF暴露下，POA-和TN- GnRH3神经元在2 dpf时神经区域均显示出明显减少，但并没有持续至3 dpf。较高的BPF剂量在2 dpf时未显示神经元大小差异，但在3 dpf时显示TN-GnRH3神经元面积减少。不同剂量的雌二醇密切模仿了BPF的这些作用。雌激素拮抗剂ICI减轻了BPF对胚胎的影响。这是第一项表明BPF通过雌激素介导的途径影响发育中的GnRH神经系统的研究。受精至受精后3天（dpf）为5和1μMBPF。在0.25μMBPF暴露下，POA-和TN- GnRH3神经元在2 dpf时神经区域均显示出明显减少，但并没有持续至3 dpf。较高的BPF剂量在2 dpf时未显示神经元大小差异，但在3 dpf时显示TN-GnRH3神经元面积减少。不同剂量的雌二醇密切模仿了BPF的这些作用。雌激素拮抗剂ICI减轻了BPF对胚胎的影响。这是第一项表明BPF通过雌激素介导的途径影响发育中的GnRH神经系统的研究。较高的BPF剂量在2 dpf时未显示神经元大小差异，但在3 dpf时显示TN-GnRH3神经元面积减少。不同剂量的雌二醇密切模仿了BPF的这些作用。雌激素拮抗剂ICI减轻了BPF对胚胎的影响。这是第一项表明BPF通过雌激素介导的途径影响发育中的GnRH神经系统的研究。较高的BPF剂量在2 dpf时未显示神经元大小差异，但在3 dpf时显示TN-GnRH3神经元面积减少。不同剂量的雌二醇密切模仿了BPF的这些作用。雌激素拮抗剂ICI减轻了BPF对胚胎的影响。这是第一项表明BPF通过雌激素介导的途径影响发育中的GnRH神经系统的研究。