ERK5 is essential for early porcine embryonic development by maintaining Endoplasmic Reticulum homeostasis

•Inhibition of ERK5 could cause ER stress during porcine embryonic development.•The protein and mRNA expression levels of ERK5 decrease at the 4-cell stage.•Sustained ER stress induces apoptosis and autophagy. Extracellular signal-regulated kinase 5 (ERK5), a mitogen-activated protein kinase (MAPK) family member, plays an important role in various biological processes, such as proliferation, apoptosis, differentiation, survival, and cell regulation. However, studies on the effects of ERK5 on porcine preimplantation embryos are limited. In this study, to determine the function of ERK5 during porcine embryo development, ERK5 function was inhibited by adding the ERK5 inhibitor JWG-071. The ERK5 mRNA and protein expression levels tended to decrease from the 4-cell stage compared to the 1-cell and 2-cell stages, suggesting that ERK5 is the maternal gene. During embryonic development in pigs, adding 5 μM of JWG-071 significantly reduced the phosphorylation of ERK5 and the blastocyst development rate (control: 53.44 ± 8.38 %; treatment: 26.65 ± 3.40 %). Additionally, ERK5 inhibition increased the expression of UPR-related proteins, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP) by inducing ER stress. Compared to the control group, the expression of the autophagy-related proteins LC3 and ATG7 was significantly increased in the ERK5 inhibition group, indicating that the inhibition of ERK5 induced autophagy. In addition, ERK5 inhibition increased the expression of BAX, a pro-apoptotic gene, resulting in apoptosis. In conclusion, the results show that ERK5 inhibition during porcine embryonic development induces autophagy and apoptosis by increasing ER stress, resulting in a negative effect on embryonic development in pigs.