Natural and synthetic progestins may pose a threat to wild fish populations living in receiving waters. In this study, the effects of norethindrone (NET) on the sex differentiation of zebrafish (Dario renio) and the mechanisms underlying these effects were investigated. Juvenile zebrafish (20 days post fertilization, pdf) were exposed to environmentally relevant concentrations (5, 50, 500, and 1000 ng L⁻¹) for 45 d. Sex ratio of the NET-exposed populations, the histology of the gonads and the transcriptional profile of the regulatory genes involved in sex differentiation and steroidogenesis were examined. The results showed that a significantly higher ratio of male/female was induced in the zebrafish populations exposed to NET at concentrations higher than 32.3 ng L⁻¹. Exposure to NET caused acceleration of sexual mature in males and a delay in ovary maturation in female zebrafish. Among the genes regulating sexual differentiation, transcripts of Dmrt1 showed a dose-dependent increase while transcripts of Figa and Fox12 showed a dose-dependent decrease in response to exposure to NET. For genes regulating the steroidogenesis, the expressions of Cyp11a1, Cyp17, Cyp19a1a, and Cyp11b were significantly down-regulated by exposure to NET, while Hsd17b3 expression was significantly up-regulated by exposure to NET at 421.3 and 892.9 ng L⁻¹. For the receptor genes in the gonads, the transcriptional expression of Pgr, Ar, and Mr was significantly up-regulated at 421.3 and 892.9 ng L⁻¹ of NET. For genes involved in the hypothalamic–pituitary axis, the transcriptional expression of Gnrh3 and Pomc was significantly up-regulated by exposure to NET with the exception for Gnrh3 at 4.2 ng L⁻¹. The results demonstrated that exposure to NET at the juvenile stage could affect gonad differentiation and sex ratio, which might be accounted for by the alterations of the transcriptional expressions of genes along the hypothalamic–pituitary–gonadal (HPG) and hypothalamic–pituitary–adrenal (HPA) axes.

天然和人工合成的孕激素可能对生活在接受水域的野生鱼类种群构成威胁。在这项研究中，研究了炔诺酮（NET）对斑马鱼（Dario renio）性别分化的影响及其潜在机制。将幼斑马鱼（受精后20天，pdf）暴露于与环境相关的浓度（5、50、500和1000 ng L ^-1）45天。NET暴露人口的性别比，性腺的组织学和参与性别分化和类固醇生成的调控基因的转录谱进行了检查。结果表明，在浓度高于32.3 ng L ^-1的NET中，斑马鱼种群中雄性/雌性的比例明显提高。。NET的暴露导致雄性性成熟的加速和雌性斑马鱼卵巢成熟的延迟。间调节性分化的基因，转录物DMRT1显示出剂量依赖性增加而转录FIGA和Fox12表明响应于暴露于NET的剂量依赖性降低。用于基因调节类固醇生成，的表达CYP11A1，CYP17，Cyp19a1a和CYP11B是通过暴露于NET显著下调，而Hsd17b3表达显著通过暴露于在NET和421.3 892.9纳克大号上调^-1。对于性腺中的受体基因，Pgr，Ar和Mr的转录表达在NET的421.3和892.9 ng L ^-1上显着上调。对于下丘脑-垂体轴相关基因，通过NET暴露，Gnrh3和Pomc的转录表达显着上调，但Gnrh3在4.2 ng L ^-1时例外。结果表明，在青少年期接受NET可能会影响性腺分化和性别比，这可能是由于下丘脑-垂体-性腺（HPG）和下丘脑-垂体-肾上腺（ HPA）轴。