The molecular mechanisms of oocyte maturation and early embryonic development are unveiling new insights into reproductive medicine

The purpose of the present review is to outline the current understanding on the molecular mechanisms governing various stages of oocyte maturation, transition from maternal to embryonic control and the initial steps of pre-embryo development. The cytoplasmic and nuclear maturation of the oocyte during pre-ovulatory development can be viewed as separate entities. Cytoplasmic maturation and the acquisition of stores of RNA and protein dominates oocyte development between the premordial and pre-ovulatory stages of development. Initiation of nuclear maturation is marked by the breakdown of the nuclear envelope, or germinal vesicle and is triggered by the midcycle luteinizing hormone peak. In vitro, this is associated with a decrease in the intracellular concentrations of cAMP. This and several subsequent steps of meiosis are controlled by the M-phase promoting factor (MPF). While the constituents of MPF, p34cdc2 kinase and B-type cyclin, are also present in mitotically dividing cells, in meiotically dividing oocytes the regulation of MPF activity differs. An oocyte-specific protein kinase, c-mos, plays an important role in up-regulating the activity of MPF at various stages of final oocyte maturation. Several lines of evidence suggest that the proper function of the c-mos-MPF system is associated with important features of the last stages of oocyte maturation such as the resumption of meiotic maturation, inhibition of DNA replication between meiosis I and II, and the maintenance of the oocyte at metaphase II arrest until it is fertilized. Eventually the destruction of c-mos and active MPF following fertilization allows the initiation of mitotic cell division in the pre-embryo. The very first cell divisions of the human pre-embryo are still under the control of maternally inherited mRNA and protein. Several lines of evidence suggest that in humans, zygotic gene expression is initiated between the 4- and 8-cell stages, after which the pre-embryo begins to utilize its own genes. Some of the first genes to be expressed in the human pre-embryo encode proteins that are associated with cell division, extracellular growth modulatory signals as well as factors associated with implantation. We acknowledge that most of the data presented comes from species other than human, therefore at present the full biological role of the proposed regulatory pathways and control mechanisms for human biology remains speculative.