Chlorpyrifos induces placental oxidative stress and barrier dysfunction by mediating mitochondrial apoptosis via the ERK/MAPK signaling pathway: In vitro and in vivo studies

Chlorpyrifos (CPF) is an organophosphorus pesticide that is widely used in agricultural production and residential environments worldwide. In this study, we determined the harmful effects and toxicological mechanism of CPF in porcine trophectoderm (pTr) cells and the placenta of female mice during pregnancy. The findings revealed that CPF significantly decreased cell viability and increased intracellular lactate dehydrogenase (LDH) release in pTr cells. Similarly, CPF induced reproductive toxicity in pregnant maternal mice, including decreased maternal, fetal, and placental weights. Moreover, after CPF treatment, pTr cells and the placenta of female mice showed significant apoptosis. JC-1 staining and flow cytometry analysis also revealed that the mitochondrial membrane potential (MMP) of pTr cells treated with CPF was significantly depolarized. Additionally, CPF can induce an increase in reactive oxygen species (ROS) and barrier dysfunction in pTr cells and the placenta of female mice. We further verified that CPF-induced mitochondrial apoptosis is mediated via the MAPK signaling pathway by measuring the changes in MAPK signaling pathway proteins and adding related inhibitors. Finally, phenotypic validation of CPF-mediated injury in pTr cells was performed by pretreatment with the inhibitor U0126, which demonstrated that CPF induced oxidative stress and barrier dysfunction in pTr cells by activating mitochondrial apoptosis through the ERK/MAPK signaling pathway. These findings suggested that exposure to CPF in early pregnancy will be a potential risk affecting placental formation and function.