Cyphenothrin disrupts the integrity of porcine trophectoderm and uterine luminal epithelial cell lines by inducing mitochondrial dysfunction and oxidative stress.

Despite the widespread use of pyrethroid insecticides in domestic, agricultural, and veterinary settings, their potential health risks, particularly those affecting female reproduction, remain a concern. Cyphenothrin, a Type II pyrethroid commonly used for household pest control and veterinary purposes, has not been well characterized with respect to female reproductive toxicity. This study therefore examined the impact of cyphenothrin on cellular processes associated with embryo implantation using immortalized porcine trophoblast and luminal epithelial (pTr and pLE) cell lines derived from gilts on gestational day 12. Cyphenothrin significantly reduced cell viability and induced apoptosis in both cell types. Mechanistically, cyphenothrin disrupted mitochondrial function, characterized by impaired oxidative phosphorylation, reduced mitochondrial membrane potential, calcium dysregulation, and increased mitophagy. Mitochondrial dysfunction led to increased mitochondrial superoxide and intracellular reactive oxygen species (ROS) levels, which subsequently triggered activation of the mitogen-activated protein kinase (MAPK) signaling pathway, thereby inducing apoptotic cell death and cell cycle inhibition. Collectively, these data demonstrate that cyphenothrin induces cytotoxicity in trophoblast and uterine epithelial cells through mitochondrial dysfunction, suggesting a potential risk for embryo implantation. Given the physiological similarities between porcine and human reproduction, these results raise concerns regarding the female reproductive toxicity of cyphenothrin in mammals, including human.