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Age-related differences in the translational landscape of mammalian oocytes. Del Llano E et al. (2020) Increasing maternal age in mammals is associated with poorer oocyte quality, involving higher aneuploidy rates and decreased developmental competence. Prior to resumption of meiosis, fully developed mammalian oocytes become transcriptionally silent until the onset of zygotic genome activation. Therefore, meiotic progression and early embryogenesis are driven largely by translational utilization of previously synthesized mRNAs. We report that genome-wide translatome profiling reveals considerable numbers of transcripts that are differentially translated in oocytes obtained from aged compared to young females. Additionally, we show that a number of aberrantly translated mRNAs in oocytes from aged females are associated with cell cycle. Indeed, we demonstrate that four specific maternal age-related transcripts (Sgk1, Castor1, Aire and Eg5) with differential translation rates encode factors that are associated with the newly forming meiotic spindle. Moreover, we report substantial defects in chromosome alignment and cytokinesis in the oocytes of young females, in which candidate CASTOR1 and SGK1 protein levels or activity are experimentally altered. Our findings indicate that improper translation of specific proteins at the onset of meiosis contributes to increased chromosome segregation problems associated with female ageing.//////////////////
Meiotic arrest and spindle defects are associated with altered KIF11 expression in porcine oocytes. Wan X et al. (2018) Kinesin superfamily proteins (KIFs) act as molecular motors and are involved in material transport along microtubules to maintain normal cellular functions. KIF11 (also named kinesin-5, Eg5, and KSP) is a plus-end-directed homotetrameric kinesin that regulates spindle formation for actuate chromosomal separation during mitosis. However, the roles of KIF11 in meiosis are still unclear. In this study, we investigated the regulatory functions of KIF11 during porcine oocyte maturation. The results indicated that KIF11 was expressed in different stages during porcine oocyte meiosis. Inhibition of KIF11 activity led to the failure of the first polar body extrusion, and we found that cell cycle progression was disturbed, which was confirmed by the decreased Cdc2 expression. Furthermore, inhibition of KIF11 resulted in decreased tubulin acetylation and caused sequential disruption of the spindle assembly and chromosome alignment. We also found that in postovulatory aging porcine oocytes, the KIF11 expression was altered, indicating that KIF11 was involved with aging-induced spindle disorganization. In summary, our results showed that KIF11 regulated the cell cycle and tubulin acetylation related spindle formation in porcine oocyte meiosis. Environ. Mol. Mutagen. 2018. © 2018 Wiley Periodicals, Inc.//////////////////
Eg5 orchestrates porcine oocyte maturational progression by maintaining meiotic organelle arrangement. Xie Y et al. (2018) Kinesin superfamily proteins are microtubule-based molecular motors essential for the intracellular transport of various cargos, including organelles, proteins, and RNAs. However, their exact roles during mammalian oocyte meiosis have not been fully clarified. Herein, we investigated the critical events during porcine oocyte meiotic maturation with the treatment of Eg5-specific inhibitor monastrol. We found that Eg5 inhibition resulted in oocyte meiotic failure by displaying the poor expansion of cumulus cells and reduced rate of polar body extrusion. In the meantime, the spindle assembly and chromosome alignment were compromised, accompanied by the decreased level of acetylated α-tubulin, indicative of less stable microtubules. Impaired actin dynamics and mitochondria integrity were also observed in Eg5-inhibited oocytes. Additionally, inhibition of Eg5 caused the abnormal distribution of cortical granules and ovastacin, a cortical granule component, potentially leading to the fertilization failure. Our findings reveal that Eg5 possesses an important function in porcine oocyte meiotic progression by regulating the organelle dynamics and arrangement.//////////////////
A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes. Clift D et al. (2015) Assembly of a bipolar microtubule spindle is essential for accurate chromosome segregation. In somatic cells, spindle bipolarity is determined by the presence of exactly two centrosomes. Remarkably, mammalian oocytes do not contain canonical centrosomes. This study reveals that mouse oocytes assemble a bipolar spindle by fragmenting multiple acentriolar microtubule-organizing centres (MTOCs) into a high number of small MTOCs to be able to then regroup and merge them into two equal spindle poles. We show that MTOCs are fragmented in a three-step process. First, PLK1 triggers a decondensation of the MTOC structure. Second, BicD2-anchored dynein stretches the MTOCs into fragmented ribbons along the nuclear envelope. Third, KIF11 further fragments the MTOCs following nuclear envelope breakdown so that they can be evenly distributed towards the two spindle poles. Failure to fragment MTOCs leads to defects in spindle assembly, which delay chromosome individualization and congression, putting the oocyte at risk of aneuploidy.//////////////////
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