Effects of 17β-estradiol (E2) on the development of zebrafish embryos

Exposure to 17β-estradiol (E2) has been shown to influence the regulation of multiple signaling pathways during development. Disruption of signaling events during early development can lead to malformations such cardiac defects. In this study we looked the expression of two genes involved in cardiac development, hand2 and lrrc10 as well as the expression of gper and cardiac development at various stages of development in zebrafish. Zebrafish embryos were exposed to concentrations of E2 (0.1μM, 2μM, 5μM, 7μM and 8μM) at 2 hours post fertilization (hpf) with subsequent measurements of lrrc10, hand2 and gper transcripts at 12hpf, 28hpf and 76hpf. Concentration dependent alteration in the expression of lrrc10, hand2 and gper was observed at 12hpf and 76hpf, but not at 28hpf. Expression of these genes were also altered after exposure to the GPER agonist G1. Expression was correlated with the formation of cardiac edema as well as other developmental abnormalities indicating a role of GPER in cardiac development.

已有研究证实，17β-雌二醇（17β-estradiol, E2）可调控发育过程中的多条信号通路。早期发育阶段的信号事件紊乱可引发心脏缺陷等畸形表型。本研究以斑马鱼为模型，检测了多个发育时期下，两个参与心脏发育的基因hand2、lrrc10以及gper的表达水平，并同步分析心脏发育状态。实验将受精后2小时（hours post fertilization, hpf）的斑马鱼胚胎暴露于不同浓度的E2（0.1μM、2μM、5μM、7μM及8μM）中，并分别在12hpf、28hpf与76hpf三个时间点，检测lrrc10、hand2及gper的转录本水平。结果显示，在12hpf与76hpf时，上述三个基因的表达呈现浓度依赖性变化，但28hpf时未观察到此类改变。经GPER激动剂G1处理后，这些基因的表达同样出现异常改变。进一步分析发现，该基因表达水平与心脏水肿及其他发育异常的形成显著相关，提示GPER在心脏发育过程中发挥关键调控作用。