Schäfers C, Teigeler M, Wenzel A, Maack G, Fenske M, Segner H
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Schmallenberg, Germany.
J Toxicol Environ Health A. 2007 May 1;70(9):768-79. doi: 10.1080/15287390701236470.
Partial or full life-cycle tests are needed to assess the potential of endocrine-disrupting compounds (EDCs) to adversely affect development and reproduction of fish. Small fish species such as zebrafish, Danio rerio, are under consideration as model organisms for appropriate test protocols. The present study examines how reproductive effects resulting from exposure of zebrafish to the synthetic estrogen 17alpha-ethinylestradiol (EE2) vary with concentration (0.05 to 10 ng EE2 L(-1), nominal), and with timing/duration of exposure (partial life-cycle, full life-cycle, and two-generation exposure). Partial life-cycle exposure of the parental (F1) generation until completion of gonad differentiation (0-75 d postfertilization, dpf) impaired juvenile growth, time to sexual maturity, adult fecundity (egg production/female/day), and adult fertilization success at 1.1 ng EE2 L(-1) and higher. Lifelong exposure of the F1 generation until 177 dpf resulted in lowest observed effect concentrations (LOECs) for time to sexual maturity, fecundity, and fertilization success identical to those of the developmental test (0-75 dpf), but the slope of the concentration-response curve was steeper. Reproduction of zebrafish was completely inhibited at 9.3 ng EE2 L(-1), and this was essentially irreversible as a 3-mo depuration restored fertilization success to only a very low rate. Accordingly, elevated endogenous vitellogenin (VTG) synthesis and degenerative changes in gonad morphology persisted in depurated zebrafish. Full life-cycle exposure of the filial (F2) generation until 162 dpf impaired growth, delayed onset of spawning and reduced fecundity and fertilization success at 2.0 ng EE2 L(-1). In conclusion, results show that the impact of estrogenic agents on zebrafish sexual development and reproductive functions as well as the reversibility of effects, varies with exposure concentration (reversibility at < or = 1.1 ng EE2 L(-1) and irreversibility at 9.3 ng EE2 L(-1)), and between partial and full life-cycle exposure (exposure to 10 ng EE2 L(-1) during critical period exerted no permanent effect on sexual differentiation, but life-cycle exposure did).
需要进行部分或全生命周期测试，以评估内分泌干扰化合物（EDCs）对鱼类发育和繁殖产生不利影响的可能性。斑马鱼等小型鱼类正被考虑用作合适测试方案的模式生物。本研究考察了斑马鱼暴露于合成雌激素17α-乙炔雌二醇（EE2）所产生的生殖效应如何随浓度（0.05至10 ng EE2 L⁻¹，标称值）以及暴露时间/持续时间（部分生命周期、全生命周期和两代暴露）而变化。亲代（F1）代直至性腺分化完成（受精后0 - 75天，dpf）的部分生命周期暴露，在EE2浓度为1.1 ng L⁻¹及更高时，损害了幼鱼生长、性成熟时间、成年鱼繁殖力（产蛋量/雌性/天）以及成年鱼受精成功率。F1代直至177 dpf的终生暴露导致性成熟时间、繁殖力和受精成功率的最低观察效应浓度（LOECs）与发育测试（0 - 75 dpf）相同，但浓度 - 反应曲线的斜率更陡。斑马鱼的繁殖在EE2浓度为9.3 ng L⁻¹时完全受到抑制，而且这基本上是不可逆的，因为经过3个月的净化后，受精成功率仅恢复到非常低的水平。相应地，净化后的斑马鱼中内源性卵黄蛋白原（VTG）合成增加以及性腺形态的退行性变化持续存在。子代（F2）代直至162 dpf的全生命周期暴露，在EE2浓度为2.0 ng L⁻¹时损害了生长、延迟了产卵开始时间并降低了繁殖力和受精成功率。总之，结果表明雌激素类药剂对斑马鱼性发育和生殖功能的影响以及效应的可逆性，随暴露浓度而变化（在≤1.1 ng EE2 L⁻¹时可逆，在9.3 ng EE2 L⁻¹时不可逆），并且在部分和全生命周期暴露之间也存在差异（关键时期暴露于10 ng EE2 L⁻¹对性别分化没有永久性影响，但全生命周期暴露则有）。
