ABSTRACT
Thus, when oocytes are considered “mature,” this comprises a number of key features associated with high developmental potential such that the oocyte can be considered:
An oocyte that has fully grown in size within a large antral follicle, which has remodeled its 1. chromatin during the growth phase prior to resumption of maturation. All maternal imprints are laid down in a time-and growth-dependent fashion and the chromatin attains a “surrounded nucleolus” confi guration, in which it is largely transcriptionally inactive before resumption of maturation (9) and forms a rim around the nucleolus, in preparation to become condensed and progress to fi rst meiosis and condense chromosomes in a chromatin conformation that mediates formation of functional centromeres/kinetochores as attachment sites and hubs of regulatory molecules for establishing a functional spindle apparatus. An oocyte that has the ability to progress to MII of nuclear maturation, has separated the 2. homologous chromosomes in a reductional division at meiosis I, and possesses a highly ordered paracrystalline MII spindle with aligned chromosomes to support normal chromatid separation at anaphase II (and not earlier than anaphase II) (25). An oocyte that not only acquires a large number of relatively inactive mitochondria but is 3. also capable of establishing polarity gradients in its ooplasm, for instance, by formation of microdomains of mitochondrial assemblies with mitochondria of high and low redox potential in the cell cortex or the vicinity of the spindle, respectively (26-28), or by recruiting molecules such as nuclear mitotic antigen (11,29), spindlin (30), nucleoplasmin, protein kinase C, glycogen synthase 3 β (31) or transcription factors such as OCT4 (9) to the meiosis II spindle such that they can reach the male chromatin by passing along microtubule tracks from the female to the male chromatin in the shortest, most effi cient, and timely manner once the oocyte has been fertilized and the oocyte spindle becomes depolymerized and pronuclei form. Thus, the meiotic spindle is thought to provide a scaffold that mediates spatial and temporal regulation of the signaling pathways orchestrating post-fertilization events. An oocyte that possesses a dense layer of cortical granules and a cytoskeleton that has medi-4. ated asymmetric division (32-35). It can be instantaneously remodeled upon sperm entry such that cortical granule exocytosis occurs (36), the membrane undergoes repetitive depolarizations, calcium transients from intracellular stores can activate the oocyte (37) and induce calcium calmodulin-dependent kinase II to release from cytostatic arrest by initiation of proteolysis of meiotic inhibitor EMI2 (early mitosis-like inhibitor 2), and, as a result, activate the anaphase promoting factor APC/C, thus mediating ubiquitinylation of cyclin B regulatory factor of maturation promoting factor (MPF) and inactivating cyclin-dependent protein kinase 1 (Cdk1 kinase) for exit from meiosis II (38,39). This sets the stage for degradation of securin, activation of separase protease, and proteolysis of meiotic cohesin protein, causing loss of cohesion between centromeres of sister chromatids, their detachment, and migration to opposite spindle poles for completion of meiosis II and fi rst polar body formation (40,41). An oocyte that has accumulated proteins, enzymes, and RNAs, in particular messenger 5. RNAs that can be stage specifi cally recruited for polyadenylation and translation during maturation or early embryogenesis according to consensus sequences in the 3′ untranslated sequence or can be degraded or stored at specifi c times to orchestrate expression and cell cycle progression and transition from oocyte to embryo (10-13). Such an oocyte should also contain a store of untranslated RNAs and enzymes involved in RNAi-mediated degradation or inactivation of messenger RNAs that modulate gene expression and chromatin conformation in the oocyte and preimplantation embryo and contribute to spindle regulation at oogenesis and control of expression during oogenesis and early embryogenesis (42-44). An oocyte embedded in an expanded cumulus that may contribute to stimulation of oocyte/6. sperm interactions and an oocyte that possesses a dense and regularly shaped zona pellucida surrounding it, which prevents polyspermic fertilization and also shelters the early embryo from mechanical stresses during passage through the ampullae, creating a microenvironment that may help to enrich molecules in the extracellular space with embryo-derived molecules (45-48).
