O-18: Epigenetic Modification of Cloned Embryo Development; State of ART

Background: At the outset of the somatic cell nuclear transfer (SCNT) process, the chromatin structure of the somatic cell which governs its state of differentiation undergoes dramatic changes, called reprogramming, and is compelled back to the embryonic stage. However, the overall epigenetic makeup of the resultant cloned embryos has been acknowledged far different from the fertilized embryos. Whether this epigenetic aberrancy in cloned embryos is a result of the state of differentiation in the somatic cell, or, the reprogramming capability of the oocyte, the resultant embryos may suffer from faulty expression and transcriptional misregulation of a great number of genes, subsequently leading to failed development. Materials and Methods: Two epigenetic approaches have been proposed to correct or complete reprogramming of the cloned embryos; 1) epigenetic modification of the somatic cell before being used for nuclear transfer, and 2) epigenetic modification of the cloned embryos after reconstitution.In this study, different epigenetic modifiers such as trichostatin (TSA), 5-aza-2΄-deoxycytidine (AzC), S-adenosylhomocysteine (SAH), and sodium butyrate (NaB) were used for epigenetic modification of nuclei donor cells and/or reconstituted embryos in cattle. Results: All tested drugs had time and dose -dependent effects on epigenetic status of somatic cells and cloned embryos. Immunocytochemistry, flowcytometery analyses of epigenetic marks and quantitative assessment of gene expression indicated that TSA, NaB, and SAH improved yield and quality of cloned embryo development, whereas, AzC had negative effects. Conclusion: The results of this study in continuation with other infield studies provide a platform to highlight the importance of assisted epigenetic modification to improve the efficiency of SCNT. However, to make a final conclusion, further studies on full term development of the resultant cloned embryos are necessary.