Yun Ji Hyeon, Kang Hyo-Gu, Choi Eun Young, Jeon Se-Been, Kim Min Ju, Jeong Pil-Soo, Song Bong-Seok, Kim Sun-Uk, Min Kwan-Sik, Sim Bo-Woong
Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea.
Division of Animal Bioscience, Graduate School of Hankyong National University, Ansung, 17579, Republic of Korea.
Sci Rep. 2025 Sep 26;15(1):32953. doi: 10.1038/s41598-025-15672-8.
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.
由于猪在生理上与人类相似，因此是人类疾病研究的重要模型，体细胞核移植（SCNT）常用于生成此类模型。然而，SCNT效率受到表观遗传重编程不完全和合子基因组激活（ZGA）不足的限制。番茄红素是一种有效的抗氧化类胡萝卜素，研究了其在体外培养（IVC）过程中改善猪胚胎发育的潜力。孤雌激活（PA）胚胎和SCNT胚胎用不同浓度的番茄红素进行培养，0.2µM显示出最显著的效果。番茄红素处理显著改善了4-5细胞期的分裂、囊胚形成、滋养外胚层和总细胞数量，同时减少了细胞凋亡。它还降低了活性氧（ROS）水平，上调了抗氧化酶相关基因（CAT、SOD1、SOD2和HO-1）的表达，并增加了4细胞期胚胎的线粒体膜电位和自噬。在表观遗传学方面，番茄红素降低了H3K4me3、H3K9me3和5mC水平，并下调了甲基转移酶相关基因（ASH2L、SUV39H2、DNMT1、DNMT3A和DNMT3B），同时上调了ZGA相关基因（ZSCAN4、UBTFL1、SUPT4H1、MYC和ELOA）。这些发现表明，IVC期间的番茄红素处理通过减少ROS相关的线粒体功能障碍、诱导自噬和改善核重编程来增强胚胎发育，从而改善猪SCNT胚胎和PA胚胎的ZGA。
