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接触波尔多液会通过性别特异性的类固醇生成改变诱导斑马鱼的生殖毒性。

Exposure to Boscalid Induces Reproductive Toxicity of Zebrafish by Gender-Specific Alterations in Steroidogenesis.

机构信息

College of Sciences, China Agricultural University, Beijing 100193, People's Republic of China.

Risk Assessment Laboratory for Bee Product Quality and Safety of Ministry of Agriculture, Institute of Agricultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, People's Republic of China.

出版信息

Environ Sci Technol. 2020 Nov 17;54(22):14275-14287. doi: 10.1021/acs.est.0c02871. Epub 2020 Nov 3.

DOI:10.1021/acs.est.0c02871
PMID:33138376
Abstract

Boscalid is a succinate dehydrogenase inhibitor fungicide and is frequently detected in surface water. Due to the frequent detection of boscalid, we evaluated its impact on the reproduction of adult zebrafish following a 21 d exposure to 0, 0.01, 0.1, and 1.0 mg/L. Following exposure to boscalid, the fertility of female zebrafish and fertilization rate of spawning eggs were reduced in a concentration-dependent manner up to a respective 87% and 20% in the highest concentration. A significant 16% reduction in the percentage of late vitellogenic oocytes was noted in ovaries, and a significant 74% reduction in the percentage of spermatids in testis was also observed after treatment with 1.0 mg/L. 17β-Estradiol (E2) concentrations decreased significantly in females (34% decrease) but significantly increased in males (15% increase) following 1.0 mg/L boscalid treatment. The expression of genes (such as , , , and ) related to the hypothalamus-pituitary-gonad-liver (HPGL) axis was significantly altered and positively correlated with E2 concentrations in female and male zebrafish ( < 0.05). Molecular docking results revealed that the binding modes between boscalid and target proteins (ER and CYP19) of zebrafish were similar to that of the reference compounds and the target proteins. The binding energies indicate that boscalid may have a weak estrogen-like binding effect or CYP19 inhibition, potentially altering the HPGL axis, thereby reducing E2 concentrations and fecundity in females. In contrast, boscalid caused significant induction of E2 steroidogenesis and subsequent feminization of gonads in males, indicating gender-specific adverse outcome pathways.

摘要

波尔多液是一种琥珀酸脱氢酶抑制剂类杀菌剂,经常在地表水检测到。由于频繁检测到波尔多液,我们评估了其对 21 天 0、0.01、0.1 和 1.0mg/L 暴露后成年斑马鱼繁殖的影响。暴露于波尔多液后,雌鱼的生育力和产卵的受精率呈浓度依赖性降低,最高浓度下分别降低了 87%和 20%。卵巢中晚期卵黄生成卵母细胞的比例显著减少了 16%,而睾丸中精子细胞的比例也显著减少了 74%。1.0mg/L 波尔多液处理后,雌鱼 17β-雌二醇(E2)浓度显著降低(降低 34%),而雄鱼 E2 浓度显著升高(升高 15%)。与下丘脑-垂体-性腺-肝(HPGL)轴相关的基因(如、、、和)的表达显著改变,并且与雌鱼和雄鱼的 E2 浓度呈正相关(<0.05)。分子对接结果表明,波尔多液与斑马鱼靶蛋白(ER 和 CYP19)的结合模式与参照化合物和靶蛋白相似。结合能表明,波尔多液可能具有较弱的雌激素样结合作用或 CYP19 抑制作用,可能改变 HPGL 轴,从而降低雌鱼的 E2 浓度和生育力。相反,波尔多液导致雄鱼 E2 类固醇生成的显著诱导和随后的性腺 feminization,表明存在性别特异性的不利结局途径。

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