Thiamethoxam Exposure Induces Endoplasmic Reticulum Stress and Affects Ovarian Function and Oocyte Development in Mice

Neonicotinoids are the most widely used insecticides in modern agriculture, and their residues have been found in the environment and food. Previous studies reported that neonicotinoids exert toxic effects in various tissues, but whether they interfered with the female reproductive process remains unknown. In our present research, thiamethoxam was selected as a representative neonicotinoid to establish a mouse toxicity model with gavage. We found that thiamethoxam decreased the ovarian coefficient and disrupted the expression of female hormone receptors, subsequently affecting follicle development. Ovarian granulosa cells from the thiamethoxam exposure group underwent a high level of apoptosis. Using transcriptome analysis, we showed that thiamethoxam exposure altered the expression of multiple oocyte genes related to inflammation, apoptosis, and endoplasmic reticulum stress. Thiamethoxam also adversely affected oocyte and embryo development. Western blotting and fluorescence staining results confirmed that thiamethoxam affected the integrity of DNA, triggered apoptosis, promoted oxidative stress and endoplasmic reticulum stress, and impaired mitochondrial function. Collectively, our results indicated that thiamethoxam exposure disrupts ovarian homeostasis and decreases oocyte quality via endoplasmic reticulum stress and apoptosis induction.