Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol‐17β on medaka embryos
Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol‐17β on medaka embryos
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纳秒脉冲电场掺入技术预测雌二醇-17β对青鳉胚胎致畸性和发育毒性的分子机制
DOI：
10.1002/jat.3579
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Tominaga N
中科院分区：
文献类型：
--
作者：
Yamaguchi A;Ishibashi H;Kono S;Iida M;Uchida M;Arizono K;Tominaga N
本文拟利用纳秒脉冲电场（nsPEF）技术研究雌二醇-17 β（E2）对青鳉（Oryzias latipes）的致畸性和胚胎发育毒性，并预测E2致畸性和胚胎发育缺陷的分子机制。将受精后5小时的胚胎暴露于10 μ mE 2和nsPEF共处理2小时，然后在非E2和nsPEF条件下连续培养直至孵化。结果表明，与对照组相比，胚胎孵化时间显著延迟，并观察到典型的异常胚胎发育，如血管形成延迟。对于DNA微阵列分析，使用在非E2和nsPEF条件下共处理2小时后连续培养的受精后6天胚胎。DNA微阵列分析在受精后6天的胚胎中鉴定了542个上调基因和1个下调基因。此外，使用差异表达基因的生物信息学分析显示，E2暴露影响各种基因本体论术语，如对激素刺激的反应。网络分析还证明，丝裂原活化蛋白激酶信号通路中的雌激素受体α可能参与调节几种转录因子，如FOX，AKT 1和表皮生长因子受体。这些结果表明，我们的nsPEF技术是一个强大的工具，评估致畸性和胚胎发育毒性的E2在青鳉胚胎，并预测其分子机制。
Herein, we propose using a nanosecond pulsed electric field (nsPEF) technique to assess teratogenicity and embryonic developmental toxicity of estradiol‐17β (E2) and predict the molecular mechanisms of teratogenicity and embryonic developmental defects caused by E2on medaka (Oryzias latipes). The 5 hour post‐fertilization embryos were exposed to co‐treatment with 10 μmE2and nsPEF for 2 hours and then continuously cultured under non‐E2and nsPEF conditions until hatching. Results documented that the time to hatching of embryos was significantly delayed in comparison to the control group and that typical abnormal embryo development, such as the delay of blood vessel formation, was observed. For DNA microarray analysis, 6 day post‐fertilization embryos that had been continuously cultured under the non‐E2and nsPEF condition after 2 hour co‐treatments were used. DNA microarray analysis identified 542 upregulated genes and one downregulated gene in the 6 day post‐fertilization embryos. Furthermore, bioinformatic analyses using differentially expressed genes revealed that E2exposure affected various gene ontology terms, such as response to hormone stimulus. The network analysis also documented that the estrogen receptor α in the mitogen‐activated protein kinase signaling pathway may be involved in regulating several transcription factors, such as FOX, AKT1 and epidermal growth factor receptor. These results suggest that our nsPEF technique is a powerful tool for assessing teratogenicity and embryonic developmental toxicity of E2and predict their molecular mechanisms in medaka embryos.