Bromuconazole impairs implantation process through cellular stress response in human trophoblast and endometrial cells

Bromuconazole, a widely used triazole-based pesticide, effectively controls fungal diseases in agriculture. Bromuconazole cause a potential toxic effect to non-target organisms and can have a negative impact on reproductive health in women, due to its long half-life and bioaccumulation ability. This study identifies the cytotoxicity and adverse effects of bromuconazole on trophoblastic cells (HTR-8/SVneo) and human endometrial cells (T HESCs), which are involved in implantation processes. The results of this study showed that 48 h of exposure to bromuconazole inhibited the viability of HTR-8/SVneo and T HESCs, and the LC50 values of each cell were identified as 28.05 mg/L and 33.41 mg/L, respectively. To identify the intracellular mechanisms of cytotoxic effects, subsequent in vitro experiments were performed after bromuconazole exposure at ≤30 mg/L concentration. 30 mg/L bromuconazole significantly induced apoptosis and cell cycle arrest after 48 h exposure through regulate the mRNA level of related factors. Bromuconazole increased reactive oxygen species accumulation and endoplasmic reticulum stress, and dysregulated MAPK (p-ERK and p-JNK) signaling. Finally, bromuconazole disrupted mitochondrial function, induced inflammation, and inhibited cell migration. These results indicate the need for more stringent regulation of the use of bromuconazole and further in vivo studies of its reproductive toxicity. This study is the first to suggest that bromuconazole adversely affect the implantation process and female reproduction.