Lycopene enhances epigenetic reprogramming and zygotic genome activation in the porcine somatic cell nuclear transfer embryo

Pigs are valuable models for human disease research due to their physiological similarities to humans, and somatic cell nuclear transfer (SCNT) is commonly used to generate such models. However, SCNT efficiency is limited by incomplete epigenetic reprogramming and insufficient zygotic genome activation (ZGA). Lycopene, a potent antioxidant carotenoid, was investigated for its potential to improve porcine embryo development during in vitro culture (IVC). Parthenogenetically activated (PA) and SCNT embryos were cultured with various lycopene concentrations, with 0.2 µM showing the most significant benefits. Lycopene treatment significantly improved 4-5-cell cleavage, blastocyst formation, trophectoderm, and total cell numbers, while reducing apoptosis. It also decreased reactive oxygen species (ROS), upregulated the expression of antioxidant enzyme-related genes (CAT, SOD1, SOD2, and HO-1), and increased mitochondrial membrane potential and autophagy in 4-cell embryos. Epigenetically, lycopene reduced H3K4me3, H3K9me3, and 5mC levels and downregulated methyltransferase-related genes (ASH2L, SUV39H2, DNMT1, DNMT3A, and DNMT3B), while upregulating ZGA-related genes (ZSCAN4, UBTFL1, SUPT4H1, MYC, and ELOA). These findings suggest that lycopene treatment during IVC enhances embryonic development by reducing ROS-related mitochondrial dysfunction, inducing autophagy, and improving nuclear reprogramming, thereby improving ZGA in porcine SCNT and PA embryos.