Epigenetic regulation of foetal development in nuclear transfer animal models

Somatic cell nuclear transfer (SCNT, 'cloning') holds great potential for agricultural applications, generation of medical model animals, transgenic farm animals or by 'therapeutic cloning' for generating human embryonic stem cells for the treatment of human diseases. However, the low survival rate of SCNT-derived pregnancies represents a serious limitation of the current technology. In order to overcome this hurdle, a deeper understanding of the epigenetic reprogramming of the somatic cell nuclei and its effect on the pregnancy is needed. Here we review the literature on nuclear reprogramming by SCNT, including studies of gene expression, DNA methylation, chromatin remodelling, genomic imprinting and X chromosome inactivation. Reprogramming of genes expressed in the inner cell mass, from which the body of the foetus is formed, seems to be highly efficient. Defects in the extra-embryonic tissues are probably the major cause of the low success rate of reproductive cloning. Methods to partially overcome such problems exist, yet more future research is needed to find practical and efficient methods to remedy this problem. Improvement of the survival of foetuses is a central issue for the future of agricultural SCNT not only for its economic viability, but also because in lack of improvements in animal welfare current regulations can block the use of the method in the EU and several other countries.