Estrogen toxicity has been an area of priority in aquatic toxicology over the last 20 years. Currently, the estrogen toxicity is primarily linked to classical estrogen signalling, ERα and ERβ, interaction. Recent evidence has indicated that a rapid, non-genomic, non-classical estrogen signaling pathway exists via the G protein coupled estrogen receptor (GPER). GPER is expressed in many biological systems, with roles in the cardiovascular system. The objective of this research was to investigate the effect of 17α-ethinylestradiol (EE2) on the heart rate of embryonic Japanese medaka (Oryzias latipes). A significant decrease (bradycardia) in embryonic heart rate was observed in all treatment concentrations (0.1 ng/L, 1 ng/L, 10 ng/L, 100 ng/L, and 1000 ng/L EE2) at 144 hpf, 168 hpf, and 192 hpf (P≤0.05). While 120 hpf and 216 hpf embryos experienced a significant a decrease from the control at 10 ng/L, 100 ng/L, and 1000 ng/L EE2, and 0.1 ng/L, 100 ng/L, and 1000 ng/L EE2 respectively (P≤0.05). Additionally, using select estrogen receptor modulators (ERMs) it was demonstrated that estrogen induced bradycardia appears to be linked to GPER and not ERα and ERβ. This research highlights GPER as a novel and alternative mode of action for EE2 toxicity at environmentally relevant concentrations. This article is protected by copyright. All rights reserved.

中文翻译：

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17α-乙炔雌二醇（EE2）对日本血Med（Oryzias latipes）心率的影响。

在过去的20年中，雌激素毒性一直是水生毒理学的重点领域。当前，雌激素毒性主要与经典的雌激素信号转导，ERα和ERβ相互作用有关。最近的证据表明，通过G蛋白偶联雌激素受体（GPER）存在着快速，非基因组，非经典的雌激素信号通路。GPER在许多生物系统中表达，并在心血管系统中起作用。这项研究的目的是调查17α-炔雌醇（EE2）对胚胎日本花aka（Oryzias latipes）心率的影响。在144 hpf，168 hpf的所有处理浓度（0.1 ng / L，1 ng / L，10 ng / L，100 ng / L和1000 ng / L EE2）下，观察到的胚胎心率均明显降低（心动过缓） ，和192 hpf（P≤0.05）。在120 ng / L，100 ng / L和1000 ng / L EE2以及0.1 ng / L，100 ng / L和1000 ng / L EE2的情况下，120 hpf和216 hpf的胚胎比对照组显着下降分别为（P≤0.05）。另外，使用选择的雌激素受体调节剂（ERM），已证明雌激素诱导的心动过缓似乎与GPER有关，与ERα和ERβ无关。这项研究强调了GPER在环境相关浓度下是EE2毒性的一种新颖的替代作用方式。本文受版权保护。版权所有。使用选择性雌激素受体调节剂（ERMs），已证明雌激素诱导的心动过缓似乎与GPER相关，与ERα和ERβ无关。这项研究强调了GPER在环境相关浓度下是EE2毒性的一种新颖的替代作用方式。本文受版权保护。版权所有。使用选择的雌激素受体调节剂（ERMs），证明雌激素诱导的心动过缓似乎与GPER相关，与ERα和ERβ无关。这项研究强调了GPER在环境相关浓度下是EE2毒性的一种新颖的替代作用方式。本文受版权保护。版权所有。