This study investigates the reprogramming mechanism and application of trophoblast replacement in monkey somatic cell nuclear transfer (SCNT). The research successfully cloned a healthy male rhesus monkey (Macaca mulatta) using a trophoblast replacement method, addressing the low efficiency of SCNT in cloning primates. The study compared SCNT and intracytoplasmic sperm injection (ICSI) embryos, revealing widespread DNA demethylation and loss of imprinting in SCNT monkey blastocysts. These defects were corrected through trophoblast replacement, leading to the successful cloning of a rhesus monkey. The findings highlight the importance of reprogramming mechanisms in SCNT and introduce a promising strategy for primate cloning. The study also identified aberrant expression of imprinted genes in SCNT embryos, which may contribute to developmental anomalies. The successful cloning of a rhesus monkey with a trophoblast replacement method demonstrates the potential of this approach in improving the efficiency of primate cloning. The study provides valuable insights into the epigenetic changes during SCNT and the role of trophoblast cells in embryo development. The results suggest that trophoblast replacement can restore normal DNA methylation patterns and improve the viability of cloned embryos. The study underscores the significance of understanding the reprogramming mechanisms in SCNT and the potential of trophoblast replacement in overcoming the challenges of cloning primates. The successful cloning of a rhesus monkey using this method highlights the importance of further research into the epigenetic regulation of SCNT and the application of trophoblast replacement in improving cloning efficiency. The study contributes to the understanding of the molecular mechanisms underlying SCNT and provides a new strategy for primate cloning. The findings have implications for the development of cloning technologies and the application of epigenetic regulators in improving the efficiency of SCNT. The study demonstrates the potential of trophoblast replacement in overcoming the challenges of cloning primates and provides a foundation for further research in this area.This study investigates the reprogramming mechanism and application of trophoblast replacement in monkey somatic cell nuclear transfer (SCNT). The research successfully cloned a healthy male rhesus monkey (Macaca mulatta) using a trophoblast replacement method, addressing the low efficiency of SCNT in cloning primates. The study compared SCNT and intracytoplasmic sperm injection (ICSI) embryos, revealing widespread DNA demethylation and loss of imprinting in SCNT monkey blastocysts. These defects were corrected through trophoblast replacement, leading to the successful cloning of a rhesus monkey. The findings highlight the importance of reprogramming mechanisms in SCNT and introduce a promising strategy for primate cloning. The study also identified aberrant expression of imprinted genes in SCNT embryos, which may contribute to developmental anomalies. The successful cloning of a rhesus monkey with a trophoblast replacement method demonstrates the potential of this approach in improving the efficiency of primate cloning. The study provides valuable insights into the epigenetic changes during SCNT and the role of trophoblast cells in embryo development. The results suggest that trophoblast replacement can restore normal DNA methylation patterns and improve the viability of cloned embryos. The study underscores the significance of understanding the reprogramming mechanisms in SCNT and the potential of trophoblast replacement in overcoming the challenges of cloning primates. The successful cloning of a rhesus monkey using this method highlights the importance of further research into the epigenetic regulation of SCNT and the application of trophoblast replacement in improving cloning efficiency. The study contributes to the understanding of the molecular mechanisms underlying SCNT and provides a new strategy for primate cloning. The findings have implications for the development of cloning technologies and the application of epigenetic regulators in improving the efficiency of SCNT. The study demonstrates the potential of trophoblast replacement in overcoming the challenges of cloning primates and provides a foundation for further research in this area.