Estrogens as immunotoxicants: 17α-ethinylestradiol exposure retards thymus development in zebrafish (Danio rerio).
Estrogens as immunotoxicants: 17α-ethinylestradiol exposure retards thymus development in zebrafish (Danio rerio).
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DOI：
10.1016/j.aquatox.2021.106025
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发表时间：
2021-11
影响因子：
4.5
通讯作者：
Larissa Kernen;Audrey Phan;Jun Bo;E. L. Herzog;J. Huynh;H. Segner;Lisa Baumann
中科院分区：
文献类型：
--
作者：
Larissa Kernen;Audrey Phan;Jun Bo;E. L. Herzog;J. Huynh;H. Segner;Lisa Baumann
雌激素性内分泌干扰物（EEDC）可引起鱼类性发育和生殖功能的改变。越来越多的证据表明，EEDC也可以干扰鱼类先天免疫的发育和功能。本研究探讨了一个潜在的破坏性影响EEDC在现场相关浓度的发展，适应性免疫，更具体地说，胸腺。斑马鱼（Danio rerio）从受精到受精后64天（dpf）暴露于环境相关浓度（3和10 ng/L）的合成雌激素17α-乙炔基雌二醇（EE 2）。暴露持续时间涵盖了胸腺从最初分化到最大生长的时期。通过组织学和形态学（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（esr 1和desr 2a）的转录水平进行了测定。EE 2暴露改变了斑马鱼的性发育（性腺分化，肝卵黄蛋白原和雌激素受体的转录水平），正如预期的那样。同时，EE 2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响应EE 2曝光，但在不同的模式比肝雌激素受体。在64天的接触期之后，将幼鱼转移到干净的水中再95天，以评估EE 2诱导效应的可逆性。研究发现，雌性斑马鱼的胸腺改变是可逆的，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，并且这种情况发生在与破坏性发育的浓度相似的浓度下。
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 (esr1andesr2a)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.