The conserved The oocytes acquire competence to undergo complex processes, oocyte growth and oocyte maturation, and the capacity for fertilization and preimplantational embryo development, by accumulating RNAs and proteins in the ooplasm. Therefore, the identification of the genes expressed in the oocyte and its functional analysis will provide valuable resources to study molecular regulatory mechanism of oocyte maturation, fertilization and early embryogenesis. To better understand these mechanisms, a decade ago, we identified a list of differentially expressed genes between GV and MII oocytes using annealing control primer (ACP)-PCR technology. Among these genes, we selected two genes, Gas6 (growth arrest-specific 6), and Sebox (skin-embryobrain- oocyte homeobox) that expressed significantly higher levels in GV than MII and analyzed its functions by using RNA interference (RNAi). Unexpectedly, and fortunately, it turned out that both of genes are new candidate of maternal effect genes (MEGs) that is important for fertilization and/or early embryogenesis but not crucial for oocyte meiotic maturation. In particular, Gas6 is essential in maintaining the proper mitochondrial function, and biosynthesis of heparan sulfate and glutathione, which are required for normal sperm chromatin decondensation, pronuclear formation, and mainly for the sufficient cytoplasmic maturation of oocytes. We suggest that the correction in the Gas6 signaling network in oocytes may improve the embryonic developmental capacity caused by deterioration of the mitochondrial functions and/or contents during oocyte maturation. Meanwhile, Sebox is crucial for zygotic genome activation (ZGA) required for subsequent embryonic development beyond the 2-cell stage by coordinating the expression of other maternal factors, such as c-mos, Gdf9, Ube2a and Wee1. In conclusion, the observed failure of fertilization after Gas6 RNAi and the embryonic development at the 2-cell stage after Sebox RNAi was similar to the loss-of-function of the previously well-known MEGs. Based on these findings, we added Gas6 and Sebox as new mammalian MEGs. Findings of our research would broaden our knowledge regarding MEGs and a field of maternal programming in oocytes.

Primary oocytes that are arrested in first meiotic prophase for years enter maturation process to meet a critical precondition for successful fertilization. During maturation, oocyte finishes meiosis I and progresses to the metaphase II stage, achieving meiotic maturity. Although importance of oocyte maturation for oocyte quality has been recognized, it is not fully understood for molecular mechanisms underlying oocyte maturation. Here, we found that dexamethasone-induced Ras-related protein 1 (RASD1), a member of RAS superfamily of small GTPases, was expressed in the mouse ovary. Immunohistochemical analysis revealed that Rasd1 expression was dominant in oocyte cytoplasm. Real-time PCR and RT-PCR analyses showed that Rasd1 mRNA was steadily expressed in germinal vesicle (GV), germinal vesicle break down (GVBD), metaphase I (MI) oocytes, but decreased in metaphase II(MII) oocytes during oocyte maturation. Konckdown of Rasd1 using RNAi system in the GV oocytes suppressed oocyte maturation through disruption of meiotic spindle and formation of misarranged chromosomes. Taken together, Rasd1 is a critical factor for MI-MII transition of oocyte and is involved in the regulation of spindle formation during oocyte maturation. Further study is needed to examine relationship between Rasd1 and spindle formation in MI-MII transition.

Cell cycle process is regulated by a number of protein kinases and among them, serine/threonine kinases carry phosphate group from ATP to substrates. The most important three kinase families are Cyclin-dependent kinase (Cdk), Polo-like kinase (Plk), and Aurora kinase. Polo-like kinase family consists of 5 members (Plk1-Plk5) and they are involved in multiple functions in eukaryotic cell division. It regulates a variety of aspects such as, centrosome maturation, checkpoint recovery, spindle assembly, cytokinesis, apoptosis and many other features. Recently, it has been reported that Plks are related to tumor development and over-expressed in many kinds of tumor cells. When injected the anti-Plk antibody into human cells, the cells show aneuploidy, and if inhibit Plks, most of the mitotic cell division does not proceed properly. For that reasons, many inhibitors of Plk have been recently emerged as new target for remedy of the cancer therapeutic research. In this paper, we reviewed briefly the characteristics of Plk families and how Plks work in regulating cell cycles and cancer formation, and the possibilities of Plks as target for cancer therapy.