Liang Yan-Qiu, Huang Guo-Yong, Lin Zhong, Li Jin, Yang Jie-Wen, Zhong Lai-Yuan, Ying Guang-Guo
Faculty of Chemistry and Environmental Science, Guangdong Ocean University, Zhanjiang, 524088, PR China.
State Key Laboratory of Organic Geochemistry, CAS Research Centre of PRD Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, 510640, PR China.
Chemosphere. 2018 Jan;190:17-24. doi: 10.1016/j.chemosphere.2017.09.127. Epub 2017 Sep 27.
The aim of this study was to assess the adverse effects of synthetic progestin norgestrel (NGT) on the reproduction of zebrafish by measuring the egg production, histology and transcriptional expression profiles along the hypothalamic-pituitary-gonadal (HPG) axis in adult zebrafish. After a pre-exposure period of 7 days, adult zebrafish were exposed to 6, 29 and 69 ng L NGT for 21 days. The results showed that exposure to 69 ng L NGT led to a significant up-regulation of follicle stimulating hormone, beta polypeptide (fshb), luteinizing hormone, beta polypeptide (lhb), progesterone receptor (pgr), estrogen receptor 1 (esr1) and androgen receptor (ar) genes in the brains, as well as significant up-regulation of hydroxysteroid 20-beta dehydrogenase (hsd20b) and hydroxysteroid 11-beta dehydrogenase 2 (hsd11b2) genes and down-regulation of 11-beta-hydroxylase (cyp11b) gene in the ovaries of females. In the testes of males, an overall down-regulation of steroidogenic acute regulatory protein (star), cytochrome P450-mediated side-chain cleavage enzyme (cyp11a1), cyp11b, hsd20b, hydroxysteroid 17-beta dehydrogenase type 3 (hsd17b3), hsd11b2 and ar genes were observed following exposure to different treatments of NGT. These transcriptional alterations imply that NGT could exhibit the potent progestogenic and androgenic activities in zebrafish. Egg production as well as histology in the ovaries and testes was not affected by NGT. Taken together, the overall results demonstrated that NGT could significantly affect transcriptional expression levels of genes related to HPG axis in zebrafish, and whether that change translates to additional physiological effects is needed further research.
本研究的目的是通过测量成年斑马鱼下丘脑-垂体-性腺（HPG）轴的产卵量、组织学和转录表达谱，评估合成孕激素炔诺酮（NGT）对斑马鱼繁殖的不良影响。在7天的预暴露期后，成年斑马鱼暴露于6、29和69 ng/L的NGT中21天。结果表明，暴露于69 ng/L的NGT导致大脑中促卵泡激素β亚基（fshb）、促黄体生成素β亚基（lhb）、孕激素受体（pgr）、雌激素受体1（esr1）和雄激素受体（ar）基因显著上调，以及雌性卵巢中20-β-羟基类固醇脱氢酶（hsd20b）和11-β-羟基类固醇脱氢酶2（hsd11b2）基因显著上调，而11-β-羟化酶（cyp11b）基因下调。在雄性睾丸中，暴露于不同处理的NGT后，观察到类固醇生成急性调节蛋白（star）、细胞色素P450介导的侧链裂解酶（cyp11a1）、cyp11b、hsd20b、17-β-羟基类固醇脱氢酶3型（hsd17b3）、hsd11b2和ar基因总体下调。这些转录改变表明NGT在斑马鱼中可能表现出强大的孕激素和雄激素活性。NGT对卵巢和睾丸的产卵量以及组织学没有影响。综上所述，总体结果表明NGT可显著影响斑马鱼中与HPG轴相关基因的转录表达水平，而这种变化是否会转化为其他生理效应还需要进一步研究。
