2,4-Dichlorophenol Increases Primordial Germ Cell Numbers via ESR2a-Dependent Pathway in Zebrafish Larvae

Yan Hu; Xuan Ma; Rongjian Liu

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2,4-Dichlorophenol Increases Primordial Germ Cell Numbers via ESR2a-Dependent Pathway in Zebrafish Larvae

机译：2,4-Dichlorophenol Increases Primordial Germ Cell Numbers via ESR2a-Dependent Pathway in Zebrafish Larvae

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Previous studies have reported the feminizing effects of 2,4-dichlorophenol (2,4-DCP) on zebrafish (Danio rerio). However, the effect of 2,4-DCP on the number of primordial germ cells (PGCs), an indicator for early sex differentiation, remains elusive. In the present study, Tg (piwil1:egf p-UTR nanos3) zebrafish (GFP-labeled PGCs) were treated with 2,4-DCP (10, 20, and 40 μg/ L) from 5 to IS days postfertilization to explore the effect on PGC numbers and to elucidate associated molecular mechanisms. The results showed that 2,4-DCP exposure increased PGC numbers, as evidenced by larger GFP fluorescent areas, upregulated expressions of PGC marker genes (vasa and dnd), and raised the female ratio. Notably, the mRNA level of estrogen receptor 2a (esr2a) was also increased subsequently. Moreover, docking studies revealed stable 2,4-DCP interactions with ESR2a, speculating a role of ESR2a signaling pathway in 2,4-DCP toxicity. Furthermore, in esr2a knockout (esr2a~(-/-)) zebrafish, the effects of 2,4-DCP were considerably minimized, proving the involvement of the ESR2a signaling pathway in the 2,4-DCP-mediated increase in PGC numbers. Dual-luciferase reporter gene assay and point mutation studies demonstrated that 2,4-DCP-stimulated promoter activity was mediated by estrogen response element (ERE) located in -686/-674 of the vasa promoter and -731/-719 of the dnd promoter. Overall, 2,4-DCP can potentially enhance the expression of vasa and dnd by binding to zebrafish ESR2a, thus leading to increased PGC numbers and subsequent female-biased sex differentiation.

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《Environmental Science & Technology: ES&T》 |2022年第19期|13878-13887|共10页
作者
Yan Hu; Xuan Ma; Rongjian Liu;
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作者单位

Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000, People's Republic of China;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类环境科学、安全科学;
关键词
2; 4-DCP; Sex differentiation; Estrogen receptor signaling; Molecular docking Estrogenic effects;

2,4-Dichlorophenol Increases Primordial Germ Cell Numbers via ESR2a-Dependent Pathway in Zebrafish Larvae

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