Epigenetic reprogramming in embryonic and foetal development upon somatic cell nuclear transfer cloning

Abstract

The birth of 'Dolly', the first mammal cloned from an adult donor cell, has sparked a flurry of research activities to improve cloning technology and to understand the underlying mechanism of epigenetic reprogramming of the transferred somatic cell nucleus. Especially in ruminants, somatic cell nuclear transfer (SCNT) is frequently associated with pathological changes in the foetal and placental phenotype and has significant consequences for development both before and after birth. The most critical factor is epigenetic reprogramming of the transferred somatic cell nucleus from its differentiated status into the totipotent state of the early embryo. This involves an erasure of the gene expression program of the respective donor cell and the establishment of the well-orchestrated sequence of expression of an estimated number of 10 000-12 000 genes regulating embryonic and foetal development. The following article reviews the present knowledge on the epigenetic reprogramming of the transferred somatic cell nucleus, with emphasis on DNA methylation, imprinting, X-chromosome inactivation and telomere length restoration in bovine development. Additionally, we briefly discuss other approaches towards epigenetic nuclear reprogramming, including the fusion of somatic and embryonic stem cells and the overexpression of genes crucial in the formation and maintenance of the pluripotent status. Improvements in our understanding of this dramatic epigenetic reprogramming event will be instrumental in realising the great potential of SCNT for basic biological research and for various agricultural and biomedical applications.

The effect of amniotic membrane stem cells as donor nucleus on gene expression in reconstructed bovine oocytes

“…Studies on pre-implantation development of SCNT embryos have shown significant deficiencies in many parts of nuclear events, including transcription and translation, epigenetic modifications such as methylation of DNA, acetylation of histones and chromatin configuration as well as genetic imprinting . In support of these observations, mammalian NT-derived embryos displayed so many abnormalities caused by aberrant expression of genes involved in early development and epigenetic reprogramming (Niemann et al, 2008). However, the amount of data collected associated with gene expression in preimplantation cloned embryos, reconstructed with AMSCs, is limited to a few genes.…”

Challenges and perspectives to enhance cattle production via in vitro techniques: focus on epigenetics and cell-secreted vesicles

“…Also, the abnormal placenta does not produce steroid hormones as it should. Finally, it is often observed abnormal embryo development when using NT or other assisted reproduction techniques and the inability to maintain alive full-term progeny mainly after NT, and these outcomes may be a result of failure during epigenetic reprogramming (NIEMANN et al, 2008;CHAVATTE-PALMER et al, 2012).…”

Mitochondrial DNA transmission and confounding mitochondrial influences in cloned cattle and pigs

“…Pre-and postnatal development is often compromised, and a variable proportion of SCNT offspring show aberrant developmental patterns and increased pre-and perinatal mortality [1]. Aberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning [2,3]. The interaction between the donor nucleus and the recipient cytoplast plays an important role in the efficiency of SCNT and may influence a number of important biological functions in SCNT during nuclear reprogramming.…”