Flufenoxuron disturbs early pregnancy in pigs via induction of cell death with ER-mitochondrial dysfunction

The use of pesticides can result in unintended side effects, such as environmental pollution and animal diseases; in serious cases, it may cause abortion. Flufenoxuron is an inhibitor of chitin synthesis that is used widely as a pesticide on farmland. It is difficult to break down and therefore accumulates in the body, and has also been detected in breast milk. Moreover, the effects of flufenoxuron in pregnancy remain elusive. Therefore, we investigated the effects of flufenoxuron on early pregnancy. Our results suggested that flufenoxuron inhibits cell development and cell cycle progression in porcine trophectoderm (pTr) cell and porcine endometrial luminal epithelial (pLE) cell lines through the repression of signal transduction pathways. Flufenoxuron induced programmed cell death through DNA fragmentation and apoptotic signals. In addition, flufenoxuron induced ROS production, ER stress, and mitochondrial malfunction; consequently, the cytosolic and mitochondrial calcium levels were increased. Expression of proteins on the ER-mitochondrial axis was increased by flufenoxuron. Cell migration was decreased by flufenoxuron treatment between pLE and pTr cells. In addition, the expression of pregnancy-related genes was decreased flufenoxuron. Collectively, our results indicated that flufenoxuron may be harmful to livestock and women in the early stages of pregnancy.