在环境相关浓度下，地屈孕酮和左炔诺孕酮对斑马鱼的大脑和眼睛具有节律性摆动的拮抗作用。
Dydrogesterone and levonorgestrel at environmentally relevant concentrations have antagonist effects with rhythmic oscillation in brain and eyes of zebrafish.
机构信息
SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China.
School of Geography, South China Normal University, Guangzhou 510631, China.
出版信息
Aquat Toxicol. 2022 Jul;248:106177. doi: 10.1016/j.aquatox.2022.106177. Epub 2022 Apr 21.
Synthetic progestins levonorgestrel (LNG) and dydrogesterone (DDG) are frequency detected in surface water. Combined effects of LNG and DDG on gonad differentiation are similar to LNG single exposure in juvenile zebrafish. However, LNG and DDG mixtures have stronger effects on spermatogenesis in testes of adult zebrafish, which show variable at different life stage. Effects of LNG and DDG mixtures on eyes and brain remain unknown. Here we investigated effects of LNG, DDG and their mixtures on eyes and brain. Zebrafish were exposed to LNG, DDG and their mixtures from 2 hpf to 144 dpf. Rhythm and vision related biological processes were enriched in eyes and brain in LNG and DDG treatments, which indicated rhythmic oscillation in eyes and brain. The qPCR data revealed that both LNG and DDG decreased transcription of arntl2 and clocka, while increased transcription of per1a, per1b, rpe65a and tefa in eyes and brain. However, DDG and LNG mixtures had slight effect on transcription of genes related to rhythm and vision. In addition, LNG and DDG reduced the thickness of inner nuclear layer in the eyes. Bliss independent model revealed that LNG and DDG had antagonist effects on transcription and histology in eyes and brain. Moreover, LNG and DDG formed the same hydrogen bonds with green-sensitive opsin-4 and rhodopsin kinase GRK7a. Taken together, LNG and DDG competed with each other for the same binding residues resulting in antagonist effect in their mixtures treatments, and have significant ecological implications to assess combined effects of progestins mixtures on fish in different organs.
合成孕激素左炔诺孕酮（LNG）和地屈孕酮（DDG）经常在地表水中被检测到。LNG 和 DDG 联合作用对幼鱼性腺分化的影响与 LNG 单一暴露相似。然而，LNG 和 DDG 混合物对成年斑马鱼睾丸的精子发生有更强的影响，这在不同的生命阶段表现出不同的变化。LNG 和 DDG 混合物对眼睛和大脑的影响仍不清楚。在这里，我们研究了 LNG、DDG 及其混合物对眼睛和大脑的影响。斑马鱼从 2 hpf 暴露于 LNG、DDG 和它们的混合物至 144 dpf。节律和视觉相关的生物过程在 LNG 和 DDG 处理的眼睛和大脑中富集，这表明眼睛和大脑中的节律性振荡。qPCR 数据显示，LNG 和 DDG 均降低了眼睛和大脑中 arntl2 和 clocka 的转录，而 per1a、per1b、rpe65a 和 tefa 的转录增加。然而，DDG 和 LNG 混合物对与节律和视觉相关的基因转录的影响较小。此外，LNG 和 DDG 减少了眼睛内核层的厚度。 Bliss 独立模型显示，LNG 和 DDG 对眼睛和大脑中基因的转录和组织学有拮抗作用。此外，LNG 和 DDG 与绿色敏感视蛋白-4 和视紫红质激酶 GRK7a 形成相同的氢键。总之，LNG 和 DDG 相互竞争相同的结合残基，导致混合物处理中的拮抗作用，并对评估不同器官中孕激素混合物对鱼类的综合影响具有重要的生态意义。
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