Gene expression during preimplantation development in the mouse embryo

Mouse preimplantation development is marked with pronounced changes in the patterns of reprogramming of gene expression during distinct transitions, namely the maternal-to-zygotic transition, compaction and blastocyst formation. This work examines RNA transcript profiles during the different stages of mouse preimplantation development. Using microarray analysis, combined with functional genomics tools such as Expression Analysis Systematic Explorer (EASE) and Ingenuity Pathway Analysis (IPA), we characterized global changes in gene expression and identified biological processes that accompany and likely underlie these transitions. This study confirmed previously described processes and events, but more important, revealed new insights. Response to DNA damage and DNA repair genes are over-represented in the oocyte and may reflect the oocyte\u27s response to selective pressures to insure genomic integrity; fertilization results in changes in the transcript profile in the 1-cell embryo that are far greater than previously recognized; and genome activation during the 2-cell stage may not be as global and promiscuous as previously proposed, but rather more selective, with genes involved in transcription and RNA processing being preferentially expressed. Further transcription profiling in 1-cell and 2-cell mouse embryos treated with transcription inhibitor α-amanitin confirmed this finding and identified genes that are activated during the course of zygotic gene activation; for example, Myc and Hdac1 could be critical players involved in genome activation and repression in the preimplantation mouse embryo. This work also reports the development of a linear mRNA amplification method from small amounts of mouse oocytes and preimplantation embryos and the subsequent generation of oocyte-specific and 8-cell-specific cDNA libraries using suppression subtractive hybridization; and these libraries were partially characterized. This work represents an extensive study on the global and temporal patterns of gene expression in the mouse oocyte and early embryo stages. The results validate this hypothesis-generating approach by identifying genes involved in critical biological processes that can now be the subject of more traditional hypothesis-driven study