Amisulbrom induces mitochondrial dysfunction, leading apoptosis and cell cycle arrest in human trophoblast and endometrial cells

Amisulbrom, a triazole-based fungicide, is utilized in agriculture to increase agricultural production by controlling Fungal infections. The long disappearance time of 50 % (DT50) and potential toxic effects of amisulbrom on nontarget organisms have been reported. However, the toxic effects on the pregnancy process remain unclear. This study aims to determine the cytotoxic responses of human trophoblast cells (HTR-8/SVneo) and human endometrial cells (T HESCs), which are associated with implantation upon amisulbrom exposure. Mitochondrial dysfunction and intracellular CA²⁺ overload were determined in both cells that are exposed to amisulbrom. Additionally, amisulbrom arrested the cell cycle progression in the G₂/M phase, causing Apoptosis and reduced survival. Excessive Reactive Oxygen Species (ROS) accumulation and dephosphorylation of PI3K/Akt signaling proteins by amisulbrom exposure mediated these toxic effects. Additionally, spheroid formation was inhibited by amisulbrom treatment in the three-dimensional hanging drop culture model. These results indicate that amisulbrom may pose an adverse effect on the implantation process. Further research is required to identify the toxicity of amisulbrom in vivo. This is the first study to raise concerns about possible toxicity mechanisms of amisulbrom in the implantation process.

Amisulbrom; Implantation; Mitochondrial function; Oxidative stress.