Effect of Sulfamethoxazole(SMZ), Trimethoprim (TMP) and Co-trimoxazole (CTX) on gene expression of human placental BeWo cell lines

Cell–cell junctions, including tight and adherens junctions, are critical for maintaining placental barrier integrity and ensuring proper maternal–fetal exchange. To investigate the impact of co-trimoxazole (CTX) as well as sulfamethoxazole (SMA) and trimethoprim (TMP) on these junctional networks, RNA sequencing was performed on BeWo placental cells exposed to non-cytotoxic concentrations of these three antibiotics for 24 h. Transcriptomic profiling revealed significant differential gene expression in sulfamethoxazole, trimethoprim and co-trimoxazole-treated cells compared to controls, with enrichment of ERK pathway that might be related to tight junctions, adherens junctions, and cell–cell adhesion. These alterations suggested disruption of placental barrier integrity. In addition, co-trimoxazole exposure was associated with activation of the ERK1/2 signaling cascade, reflected by downregulation of multiple dual-specificity phosphatase (DUSP) genes that normally suppress MAPK activity. Together, the RNA-seq findings indicate that CTX interferes with barrier-related gene networks and promotes ERK pathway activation, supporting its potential to compromise placental barrier function.