Somatic cell nuclear transfer in domestic and wild ruminants: Overcoming epigenetic barriers to improve cloning efficiency and biodiversity conservation

Abstract

Somatic cell nuclear transfer (SCNT) is a powerful reproductive biotechnology with wide-ranging applications in livestock breeding, biodiversity conservation, regenerative medicine, and developmental biology. Despite remarkable progress in mammalian cloning, the efficiency of SCNT remains low, particularly in wild ruminants, as only a small proportion of reconstructed embryos develop to terms. There is growing evidence that incomplete epigenetic reprogramming, including aberrant DNA methylation, histone modifications, and dysregulated embryonic gene expression, is a key factor in developmental failure and postnatal abnormalities. This review provides a comprehensive overview of recent advances in SCNT in domestic and wild ruminants, covering donor cell selection, oocyte competence, nuclear reprogramming, embryonic development, placental abnormalities, pregnancy loss, and offspring health. It also summarizes current strategies aimed at improving cloning efficiency through epigenetic modulation and the optimization of SCNT protocols. Special attention is given to the challenges associated with applying SCNT to wild ruminant species, where limited access to high-quality gametes and donor cells, combined with species-specific reproductive limitations, further compromise the success of cloning. Finally, the technical and biological challenges that still limit the routine application of SCNT were analyzed, and the importance of future research on characterizing donor cells, cell cycle synchronization, and epigenetic reprogramming was highlighted.