Dietary exposure of 17-alpha ethinylestradiol modulates physiological endpoints and gene signaling pathways in female largemouth bass (Micropterus salmoides). Micropterus salmoides

17alpha-ethinylestradiol (EE2), used for birth control in humans, is a potent estrogen that is found in wastewater at low concentrations (ng/L). EE2 has the ability to interfere with the endocrine system of fish, affecting reproduction which can result in population level effects. The objective of this study was to determine if dietary exposure to EE2 would alter gene expression patterns and key pathways in the liver and ovary and whether these could be associated with reproductive endpoints in female largemouth bass (LMB) during egg development. Female LMB received 70 ng EE2/g feed (feed administered at 1% of body weight) for 60 days. EE2 dietary exposure significantly reduced plasma vitellogenin concentrations by 70%. Hepatosomatic and gonadosomatic indices were also decreased with EE2 feeding by 38.5% and 40%, respectively. Transcriptomic profiling revealed that there were more changes in steady-state mRNA levels in the liver compared to the ovary. Genes associated with reproduction were differentially expressed such as vitellogenin in the liver and aromatase in the gonad. In addition, a set of genes related with oxidative stress (e.g., glutathione reductase and glutathione peroxidase) were identified as altered in the liver and genes associated with the immune system (e.g., complement component 1, and macrophage-inducible C-type lectin) were altered in the gonad. In a follow-up study with 0.2 ng EE2/g feed for 60 days, similar phenotypic and gene expression changes were observed that support these findings with the higher concentrations. This study provides new insights into how dietary exposure to EE2 interferes with endocrine signaling pathways in female LMB during a critical period of reproductive oogenesis. Overall design: Dietary exposure to EE2 would alter gene expression patterns and key pathways in the liver and ovary and these could be associated with reproductive endpoints in female largemouth bass during maturation. Female LMB received about 351 ng EE2 per day (from EE2-laced feed containing 70ng EE2/g feed) for 60 days.

17α-乙炔雌二醇（17alpha-ethinylestradiol, EE2）是一种用于人类避孕的强效雌激素，在废水中以纳克/升（ng/L）级别的低浓度存在。EE2可干扰鱼类内分泌系统，影响其繁殖过程，进而引发种群水平的生态效应。本研究旨在探究膳食暴露EE2是否会改变雌性大口黑鲈（largemouth bass, LMB）在卵子发育过程中肝脏与卵巢的基因表达模式及关键通路，且这些变化是否与其繁殖终点相关。实验中，雌性大口黑鲈以每克饲料含70 ng EE2的饵料（投喂量为其体重的1%）进行为期60天的膳食暴露。结果显示，膳食暴露EE2可使雌性大口黑鲈的血浆卵黄蛋白原浓度显著降低70%；同时其肝体指数与性腺指数分别下降38.5%与40%。转录组分析表明，与卵巢相比，肝脏中的稳态mRNA水平变化更为显著。与繁殖相关的基因呈现差异表达，例如肝脏中的卵黄蛋白原基因以及性腺中的芳香化酶基因。此外，肝脏中鉴定出一批与氧化应激相关的差异表达基因（如谷胱甘肽还原酶、谷胱甘肽过氧化物酶），而性腺中则发现与免疫系统相关的差异表达基因（如补体成分1、巨噬细胞诱导型C型凝集素）。在后续采用每克饲料含0.2 ng EE2的饵料开展的60天暴露实验中，研究人员观察到了相似的表型与基因表达变化，验证了高浓度暴露下的实验结果。本研究为膳食暴露EE2如何在雌性大口黑鲈繁殖卵子发生的关键时期干扰内分泌信号通路提供了全新的认识。实验整体设计：膳食暴露EE2可改变雌性大口黑鲈肝脏与卵巢的基因表达模式及关键通路，且这些变化与其成熟过程中的繁殖终点相关。实验中，雌性大口黑鲈每日摄入约351 ng EE2（来自每克含70 ng EE2的饵料），暴露时长为60天。