关键词: AlphaFold2 earthworms estrogen receptor reproductive health triazole fungicide

Mesh : Animals Oligochaeta / drug effects genetics metabolism Reproduction / drug effects Fungicides, Industrial / toxicity chemistry Triazoles / toxicity chemistry Stereoisomerism Soil Pollutants / toxicity chemistry Female Receptors, Estrogen / metabolism genetics Estrogens / metabolism toxicity

来  源:   DOI:10.1021/acs.jafc.4c04168

Abstract:
Widespread use of the new chiral triazole fungicide mefentrifluconazole (MFZ) poses a threat to soil organisms. Although triazole fungicides have been reported to induce reproductive disorders in vertebrates, significant research gaps remain regarding their impact on the reproductive health of soil invertebrates. Here, reproduction-related toxicity end points were explored in earthworms (Eisenia fetida) after exposure for 28 d to soil containing 4 mg/kg racemic MFZ, R-(-)-MFZ, and S-(+)-MFZ. The S-(+)-MFZ treatment resulted in a more pronounced reduction in the number of cocoons and juveniles compared to R-(-)-MFZ treatment, and the expression of annetocin gene was significantly downregulated following exposure to both enantiomers. This reproductive toxicity has been attributed to the disruption of ovarian steroidogenesis at the transcriptional level. Further studies revealed that MFZ enantiomers were able to activate the estrogen receptor (ER). Indirect evidence for this estrogenic effect is provided by the introduction of 17β-estradiol, which also induces reproductive disorders through ER activation.
摘要:
新的手性三唑类杀菌剂甲氟康唑(MFZ)的广泛使用对土壤生物构成威胁。尽管据报道,三唑类杀菌剂会引起脊椎动物的生殖障碍,关于它们对土壤无脊椎动物生殖健康的影响,仍然存在显著的研究空白。这里,在暴露于含有4mg/kg外消旋MFZ的土壤28d后,在蚯蚓(Eiseniafetida)中探索了与生殖相关的毒性终点,R-(-)-MFZ,和S-(+)-MFZ。与R-(-)-MFZ治疗相比,S-(+)-MFZ治疗导致茧和幼体数量更明显的减少,并且在暴露于两种对映异构体后,Annetocin基因的表达显着下调。这种生殖毒性归因于转录水平的卵巢类固醇生成的破坏。进一步的研究表明,MFZ对映体能够激活雌激素受体(ER)。通过引入17β-雌二醇提供了这种雌激素作用的间接证据,它也通过ER激活诱导生殖障碍。
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