Expression of imprinted genes in human preimplantation development

Imprinted gene expression in preimplantation development has been extensive ly studied in the mouse. Different imprinted genes vary in their time of on set of expression and also in the timing and tissue-specificity of mono-all elic expression. We have surveyed a range of imprinted genes for expression , and mono-allelic expression. in human development. Due to the scarcity of human embryos available for research, we first prepared amplified cDNA fro m replicate samples of human oocytes, four-cell. eight-cell and blastocyst stages. We then analysed these cDNAs for expression of a range of imprinted genes. Three of six genes analysed (SNRPN. PEG1 and UBE3A) are clearly exp ressed in preimplantation embryos. Expression was confirmed by direct analy sis of embryos for these genes. For one of the expressed genes, SNRPN. we h ave shown that expression is mono-allelic from the paternal allele in human preimplantation embryos, This gene is also mono-allelically expressed in m ouse preimplantation embryos. In our earlier work, we investigated the mole cular mechanisms governing mono-allelic expression of the paternal allele o f the Xist gene in preimplantation mouse embryos. We found that mono-alleli c expression was correlated with differential methylation of Xist promoter sites in egg and sperm. and specific binding of a protein only to the methy lated maternal (egg) allele. However, extension of these Studies to the hum an showed that, unlike the mouse, XIST is expressed front both parental all eles in human preimplantation embryos. Since perturbation of imprinting is associated with disease and tumourigenesis. it is important to know the exp ression profiles of imprinted genes in human embryos and to monitor for nor mal imprinted gene expression with the introduction of new procedures in as sisted conception. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.