Faculty of Science, Ontario Tech University, Oshawa Ontario, Canada.
Environ Toxicol Chem. 2020 Apr;39(4):904-912. doi: 10.1002/etc.4691. Epub 2020 Mar 22.
Estrogen toxicity has been an area of priority in aquatic toxicology over the last 20 yr. Currently, estrogen toxicity is primarily linked to classical estrogen signaling, the interaction of estrogen receptors alpha and beta (ERα and ERβ). Recent evidence has indicated that a rapid, nongenomic, nonclassical estrogen signaling pathway exists via the G protein-coupled estrogen receptor (GPER), which is expressed in many biological systems, with roles in the cardiovascular system. The objective of the present study 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 at all treatment concentrations (0.1, 1, 10, 100, and 1000 ng/L EE2) at 144, 168, and 192 h postfertilization (hpf; p ≤ 0.05), whereas 120 and 216 hpf embryos experienced a significant decrease from the control at 10, 100, and 1000 ng/L EE2 and 0.1, 100, and 1000 ng/L EE2, respectively (p ≤ 0.05). In addition, using select estrogen receptor modulators, it was demonstrated that estrogen-induced bradycardia appears to be linked to GPER and not ERα and ERβ. The present study highlights GPER as a novel and alternative mode of action for EE2 toxicity at environmentally relevant concentrations. Environ Toxicol Chem 2020;39:904-912. © 2020 SETAC.
在过去的 20 年中，雌激素毒性一直是水生毒理学的一个重点研究领域。目前，雌激素毒性主要与经典的雌激素信号传导、雌激素受体 alpha 和 beta（ERα 和 ERβ）的相互作用有关。最近的证据表明，一种快速的、非基因组的、非经典的雌激素信号通路存在于 G 蛋白偶联雌激素受体（GPER）中，GPER 在许多生物系统中表达，在心血管系统中发挥作用。本研究的目的是研究 17α-乙炔基雌二醇（EE2）对胚胎日本青鳉（Oryzias latipes）心率的影响。在受精后 144、168 和 192 小时（hpf；p≤0.05），所有处理浓度（0.1、1、10、100 和 1000ng/L EE2）下，胚胎心率均显著下降（心动过缓），而 120 和 216 hpf 胚胎在 10、100 和 1000ng/L EE2 和 0.1、100 和 1000ng/L EE2 时与对照组相比心率显著下降（p≤0.05）。此外，使用选择性雌激素受体调节剂表明，雌激素诱导的心动过缓似乎与 GPER 有关，而与 ERα 和 ERβ 无关。本研究强调了 GPER 作为一种新的和替代的作用模式，用于环境相关浓度下的 EE2 毒性。环境毒理化学 2020；39：904-912。©2020 SETAC。
