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Updated: Aug 21, 2026

Measuring Rates of Herbicide Metabolism in Dicot Weeds with an Excised Leaf Assay
Published on: September 7, 2015
Herbicides as Isoform-Selective Inhibitors of Human 3β-HSD1 and Rat 3β-HSD4: Structure-Activity Relationships and
Huiyi Che1,2, Xiya Ren1,2, Shaowei Wang1,2
1Reproductive Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang325027, China.
Abstract:
Environmental exposure to herbicides has raised significant concerns. However, whether herbicides affect placental 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) remains unclear. This study investigated the inhibitory effects of 14 herbicides, especially dinitroanilines, on human (h3β-HSD1) and rat (r3β-HSD4), key enzymes in progesterone biosynthesis. In vitro assays showed isopropalin and oryzalin potently inhibited h3β-HSD1 (IC50 39.56 and 52.99 μM) via mixed-type inhibition. Inplacental JAr cells, oryzalin and profluraline suppressed progesterone synthesis at 100 μM, while isopropalin had no effect. Species-dependent inhibition was observed; oryzalin was most potent against r3β-HSD4 (IC50 33.52 μM), and cyanazine also inhibited the rat isoform. Molecular docking indicated their binding to the NAD+-binding pocket. SAR and pharmacophore modeling identified molecular volume and flexibility as key for h3β-HSD1 potency. Network toxicology linked herbicide exposure to recurrent pregnancy loss via steroidogenic genes. These findings provide mechanistic evidence that specific herbicides disrupt progesterone production and may contribute to adverse reproductive outcomes.
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