Resmethrin induces implantation failure by disrupting calcium homeostasis and forcing mitochondrial defects in porcine trophectoderm and uterine luminal epithelial cells.

Resmethrin, a type I pyrethroid insecticide, is frequently used globally in residential and farmland areas to control pests. Owing to the repeated administration of resmethrin, and particularly because of its lipophilic nature, residues have been detected in various environments, crops, and livestock. Previous studies have shown the adverse effects of resmethrin, including neurotoxicity and hepatotoxicity. However, the toxic effects of resmethrin on the female reproductive system have rarely been investigated. In the present study, we used two cell types, porcine trophectoderm (pTr) and porcine uterine luminal epithelial (pLE) cells, to examine the toxic effects of resmethrin on implantation and its mechanisms. Our study showed that resmethrin exposure induced apoptosis and inhibited cell cycle progression, thereby reducing the viability of both cell types. In addition, calcium homeostasis was disrupted following resmethrin treatment, and disrupted calcium homeostasis impaired the mitochondrial membrane potential and mitochondrial respiration. In addition to mitochondrial dysfunction, GRP75 and ER stress-related proteins were upregulated. Furthermore, the AKT and MAPK cascades were altered, and reactive oxygen species production and inflammation occurred after resmethrin treatment. Ultimately, through various mechanisms, resmethrin decreased the migratory abilities, and it could diminish the crosstalk between the two cell lines and lower the probability of successful implantation. Overall, we demonstrated that resmethrin interfered with the implantation process by triggering various toxic mechanisms. This study presents, for the first time, evidence regarding the mechanisms through which resmethrin exerts toxic effects on the female reproductive system, thereby raising awareness regarding the potential implications of its widespread use.