In humans, early embryo development is a complex process that consists of sequential maturation events of the oocyte, fertilization and embryo growth (4-cell, 8-cell, morula and blastocyst). Indeed, oocytes and spermatozoa are atypical, highly specialized cell types compared to somatic cells. Yet, after fertilization, a zygote is formed, the ultimate totipotent cell that can be considered to be the ultimate undifferentiated cell type, as it gives rise to all cell types and live offspring. Totipotency persists for the very first cell doublings, from the single cell and zygote to at least the 4-cell pre-embryo. Initiation of transcription in the newly-formed embryonic genome reportedly occurs at the 4- and 8-cell stage (Braude et al., 1988
). A few studies have documented key events that follow fertilization in humans such as decreases in abundance of individual mRNAs (Taylor et al., 2001
), overall patterns of gene expression in individual human oocyte and preimplantaion embryos stage (Dobson et al., 2004
), and more generalizable transcription profiles of pooled morphologically normal human oocytes and embryos (Zhang et al., 2009
). These data provide fundamental resources for understanding the genetic network controlling the early stages of human embryo development. At the morula stage, the human pre-embryo undergoes compaction, with the loss of the cellular distinction between the blastomeres. This is followed by the high expression of genes involved in tight intercellular junctions. Then, when the human embryo has reached the 35- to 65-cell stage, the trophoblast cells pump nutrients and water into the interior of the cell-sphere, forming a blastocyst, within which the inner cell mass (ICM) cells continue to proliferate. It is at the blastocyst stage that ICM cells are harvested for the derivation of embryonic stem (ES) cells (Reubinoff et al., 2000
; Thomson et al., 1998
). Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro
in an undifferentiated state as human embryonic stem cells (hESCs). hESCs are remarkable in their ability to generate virtually any cell type; hence they carry many hopes for cell therapy. Human mature MII oocytes, as well as hESCs, are able to achieve the feat of cell reprogramming towards pluripotency, either by somatic cell nuclear transfer or by cell fusion, respectively (Cowan et al., 2005
; Hochedlinger et al., 2004
; Saito et al., 2008
; Sung et al., 2006
). Knowledge gathered from the field of ESCs was at the heart of the groundbreaking discovery that both mouse and human somatic cells can be reprogrammed into a pluripotent state by defined factors. The field of induced pluripotent stem cells (iPSCs) has marked a new era in stem cell research, and has also provided data pertinent to improving the understanding of pluripotency (Takahashi et al., 2007
; Yu et al., 2007
). Since totipotency and pluripotency are at the center of early embryonic development, comprehending their molecular mechanisms is crucial to our understanding of reproductive biology and to regenerative medicine.
DNA microarray technology is one of the most widely used and potentially revolutionary research tools derived from the human genome project (Venter et al., 2001
). This technology provides a unique tool for the determination of gene expression at the level of messenger RNA (mRNA) on a genomic scale. Its capacity has opened new paths for biological investigation and generated a large number of applications (Stoughton. 2005
), including the analysis of the transcriptomic profiles from early embryo development and the identification of new prognostic biomarkers for use in the in vitro
fertilization (IVF) program (Hamatani et al., 2004a
; Assou et al., 2008
). The application of microarray technology to the analysis of human oocyte and early embryo cleavage poses specific challenges associated with the picogram levels of mRNA in a single oocyte and embryo, the plasticity of the embryonic transcriptome, the scarcity of the material and ethical considerations.
In this review we analyzed data from published reports and include our own data to define the genomic profile during early embryonic development. Once the molecular signature is established, biomarkers can be identified on a large scale, validated and tested prior to clinical applications for embryo selection to improve single embryo transfer (SET) programs. Such a research workflow should provide an understanding of the molecular and cellular mechanisms of oocyte and embryo function, as well as important insights for the development of diagnostic tests for oocyte quality and embryo competence.