Key Laboratory of Aquaculture in the South China Sea for Aquatic Economic Animal of Guangdong Higher Education Institutes, Fisheries College, Guangdong Ocean University, Zhanjiang, 524088, PR China; Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, Fisheries College, Guangdong Ocean University, Zhanjiang, 524088, PR China.
Key Laboratory of Aquaculture in the South China Sea for Aquatic Economic Animal of Guangdong Higher Education Institutes, Fisheries College, Guangdong Ocean University, Zhanjiang, 524088, PR China.
Chemosphere. 2023 Jan;310:136844. doi: 10.1016/j.chemosphere.2022.136844. Epub 2022 Oct 14.
Norethisterone (NET), one of the synthetic progestins, is detected with increasing frequency in the water environment and distributed in the ocean, with a potential toxicity risk to marine organisms. However, current studies on the adverse effects of progestins (including NET) in aquatic environments have focused on freshwater organisms, mainly fish. In the present, marine medaka (Oryzias melastigma) larvae were exposed to 91.31 ng/L NET for 10 days, and then the swimming behavior, oxidation-antioxidant-related enzyme activities, sex and thyroid hormone levels, and the gene transcription patterns of the larvae were measured. After NET treatment, medaka larvae were raised in artificial seawater until 5 months of age, and the sex ratio was counted. Ten-day exposure to 91.31 ng/L NET inhibited swimming behavior, of marine medaka larvae, which showed that the time in the resting state was significantly prolonged, while the time in the large motor state was significantly reduced; disrupted oxidative-antioxidant system, significantly up-regulated the enzymatic activities of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px); affected the hormone levels of larvae, lowered 11- keto testosterone (11-KT) and triiodothyronine (T3) concentrations. RNA-seq results showed that 91.31 ng/L NET exposure for 10 days changed the transcript levels of 275 genes, of which 28 were up-regulated and 247 were down-regulated. Differentially expressed genes (DEGs) were mainly significantly enriched in piwi interacting RNA (piRNA), gonadal development, gametogenesis, and steroidogenesis biological processes, etc. After removing NET exposure and returning to breeding for 140 days, a significant increase in male proportions (69.67%) was observed in sexually mature medaka populations in the NET-treated group. These results show that exposure to 91.31 ng/L NET for 10 days can lead to various adverse effects on marine medaka larvae. These findings shed light on the potential ecological risks of synthetic progestins to marine organisms.
去甲孕酮（NET）是一种合成孕激素，在水环境中被检测到的频率越来越高，分布于海洋中，对海洋生物具有潜在的毒性风险。然而，目前关于环境中孕激素（包括 NET）的不良影响的研究主要集中在淡水生物上，主要是鱼类。本研究采用海洋原种稻蝗（Oryzias melastigma）幼体，暴露于 91.31ng/L NET 中 10 天，检测幼体的游泳行为、氧化应激相关酶活性、性别和甲状腺激素水平以及幼体的基因转录模式。NET 处理后，将稻蝗幼体在人工海水中饲养至 5 月龄，统计性别比例。10 天 91.31ng/L NET 暴露抑制了海洋原种稻蝗幼体的游泳行为，表现为静止状态时间明显延长，而大运动状态时间明显减少；破坏了氧化应激系统，显著上调了活性氧（ROS）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）的酶活性；影响了幼体的激素水平，降低了 11-酮睾酮（11-KT）和三碘甲状腺原氨酸（T3）的浓度。RNA-seq 结果表明，暴露于 91.31ng/L NET 10 天可改变 275 个基因的转录水平，其中 28 个基因上调，247 个基因下调。差异表达基因（DEGs）主要显著富集在 piwi 相互作用 RNA（piRNA）、性腺发育、配子发生和类固醇生成等生物学过程中。去除 NET 暴露并在暴露后 140 天恢复繁殖后，在 NET 处理组中，性成熟稻蝗种群的雄性比例（69.67%）显著增加。这些结果表明，暴露于 91.31ng/L NET 10 天可导致海洋原种稻蝗幼体产生各种不良影响。这些发现揭示了合成孕激素对海洋生物的潜在生态风险。
