Epigenetic regulation in mammalian preimplantation embryo development

Starting from fertilization and ending with implantation, preimplantation embryo development can be divided into several well-orchestrated stages: fertilization, cell cleavage, morula and blastocyst formation. Understanding the stages of preimplantation development and the underlying regulatory molecular mechanisms is of pivotal importance for basic reproductive biology and for practical applications including regenerative medicine. To decipher the regulatory mechanisms, determining the global gene, RNA and protein expression patterns of early embryo is indispensable. Early attempts to do this provided data on protein expression patterns using comparative electrophoretic analysis with radiolabeled tyrosine and lysine [1] and RNA expression patterns were estimated using cDNA library analysis [2]. A series of subsequent studies reported modified or novel methods including polymerase chain reaction (PCR)-based differential display [3] and subtractive cDNA library construction techniques [4]. With the development of microarray technology, microarray analysis soon became one of the most powerful approaches, providing more comprehensive and precise global expression pattern data, especially on gene expression profiles [5-7]. Based on transitions in gene expression patterns in mouse embryos, preimplantation development can also be divided into several phases: phase I from fertilization to the 2-cell stage; phase II from the 4-cell to the 8-cell stage and phase III from the 8-cell embryo to the blastocyst stage. Phases I and II can also be called zygotic genome activation (ZGA) and mid-preimplantation gene activation, respectively [8]. At ZGA, some proteins originally formed in the stage of oogenesis remain after fertilization and contribute to the regulation of the next developmental processes.Preimplantation embryo development is regulated both genetically and epigenetically. Based on the knowledge of genetic profiles, studies proceeded to elucidate epigenetic profiles in