Estrogenic endocrine disrupting compounds (EEDCs) can cause alterations in sexual development and reproductive function of fish. Growing evidence suggests that EEDCs can also interfere with development and function of innate immunity of fish. The present study examined a potential disruptive effect of EEDCs at field-relevant concentrations on the development of adaptive immunity, more specifically the thymus. Zebrafish (Danio rerio) were exposed from fertilization until 64 days post-fertilization (dpf) to environmentally relevant (3 and 10 ng/L) concentrations of the synthetic estrogen 17α-ethinylestradiol (EE2). The exposure duration covered the period of initial thymus differentiation to maximum growth. Thymus development was assessed by histological and morphometric (thymus area) analysis, thymocyte number, and transcript levels of thymocyte marker genes. Additionally, transcript levels of the estrogen receptors (esr1 and esr2a) were determined. The EE2 exposure altered sexual development (gonad differentiation, transcript levels of hepatic vitellogenin and estrogen receptors) of zebrafish, as expected. At the same time, the EE2 treatment reduced the thymus growth (thymus area, thymocyte number) and transcript levels of thymus marker genes. The expression of the thymic estrogen receptors responded to the EE2 exposure but in a different pattern than the hepatic estrogen receptors. After the 64-day-exposure period, the juvenile fish were transferred into clean water for another 95 days to assess the reversibility of EE2-induced effects. The thymic alterations were found to be reversible in female zebrafish but persisted in males. The present study provides the first evidence that the development of the fish adaptive immune system is sensitive to EEDCs, and that this takes place at concentrations similar to those that disrupt sexual development.

雌激素内分泌干扰化合物 (EEDC) 可导致鱼类性发育和生殖功能的改变。越来越多的证据表明，EEDCs 还可以干扰鱼类先天免疫的发育和功能。本研究检查了 EEDC 在与场相关的浓度下对适应性免疫发展的潜在破坏性影响，更具体地说是胸腺。斑马鱼（斑马鱼) 从受精到受精后 64 天 (dpf) 暴露于环境相关（3 和 10 ng/L）浓度的合成雌激素 17α-炔雌醇 (EE2)。暴露持续时间涵盖最初胸腺分化至最大生长的时期。通过组织学和形态计量学（胸腺面积）分析、胸腺细胞数量和胸腺细胞标记基因的转录水平评估胸腺发育。此外，雌激素受体（ esr1和esr2a）的转录水平被确定。正如预期的那样，EE2 暴露改变了斑马鱼的性发育（性腺分化、肝卵黄素和雌激素受体的转录水平）。同时，EE2 处理降低了胸腺生长（胸腺面积、胸腺细胞数量）和胸腺标记基因的转录水平。胸腺雌激素受体的表达对 EE2 暴露有反应，但与肝脏雌激素受体的表达方式不同。在 64 天的暴露期后，将幼鱼转移到干净的水中再过 95 天，以评估 EE2 诱导效应的可逆性。发现胸腺改变在雌性斑马鱼中是可逆的，但在雄性斑马鱼中持续存在。本研究提供了第一个证据表明鱼类适应性免疫系统的发育对 EEDC 敏感，