孕激素甲炔诺酮对斑马鱼的甲状腺内分泌干扰机制研究

孕激素物质广泛应用于人类口服避孕药和激素替代疗法以及畜牧养殖业中，因其高生物活性而受到了人们的广泛关注。目前大多数的研究都报道了孕激素对鱼类的生殖毒性，而对其甲状腺内分泌干扰效应及其作用机制研究非常有限。因此，本项目将以环境中检出浓度高和活性很强的甲炔诺酮为目标化合物，以斑马鱼为实验动物模型，对斑马鱼开展长期暴露实验，探讨孕激素物质对斑马鱼甲状腺结构和功能的影响，并绘制斑马鱼在孕激素暴露下的转录和蛋白表达图谱，筛选出响应孕激素甲状腺内分泌干扰效应的关键基因，进而阐明孕激素物质对斑马鱼甲状腺内分泌干扰效应产生的分子机理，以此为评价孕激素的潜在生态健康风险和环保决策提供科学依据。

Progestins are widely used in oral contraceptives and hormone replacement therapy in humans, as well as in the livestock industry. And they have drawn extensive attention because of the high biological activities. Until recently, most studies have reported the reproductive effects of progestins in fish, less on the effects of progestins on thyroid. Therefore, this project aims to investigate the effects of long-term exposure of the progestin (norgestrel) on thyroid structure and function in zebrafish, and to map the transcription and protein expression profiles after exposure to progestins in zebrafish, and to screen key genes for the effects on thyroid. The results from this project can elucidate the molecular mechanism of the effects of progestins on thyroid. Finally, these results will provide a scientific basis of progestins to evaluate the potential ecological health risks and environmental decision-making.