Novel Insights into Stereoselective Reproductive Toxicity Induced by Mefentrifluconazole in Earthworms ( Eisenia fetida ): First Report of Estrogenic Effects.

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.