Article
Aurora kinase B, epigenetic state of centromeric heterochromatin and chiasma resolution in oocytes

https://doi.org/10.1016/S1472-6483(10)60169-1Get rights and content

Abstract

Aurora kinases comprise a family of phosphoproteins performing multiple functions in mitosis and meiosis. Because Aurora kinase B (AURKB) expression is altered in aged oocytes and there is only limited information on its function in meiosis, it was decided to study the spatial distribution and co-localization of AURKB with other regulatory proteins at centromeres during mouse oocyte maturation. AURKB associates with chromosomes after germinal vesicle breakdown, is enriched at centromeres from prometaphase I and transits to the spindle midzone at late anaphase I. Preferential inhibition of AURKB by low concentrations of ZM 447439 inhibitor prevents polar body formation and affects spindle formation and chromosome congression at meiosis I, associated with expression of BubR1 checkpoint protein at kinetochores. Release of cohesion between sister chromatids appears inhibited resulting in failure of chiasma resolution in oocytes progressing to anaphase I. Concomitantly, the inhibitor reduces histone H3 lysine 9 trimethylation at centromeric heterochromatin and affects chromosome condensation. The cytokinesis arrest protects young, healthy oocytes from errors in chromosome segregation although increasing polyploidy. This study shows that changes in activity of AURKB may increase risks for chromosome non-disjunction and aneuploidy in mammalian oocytes, irrespective of age.

Section snippets

Ursula Eichenlaub-Ritter has been Professor for Cell Biology at the University of Bielefeld, Department of Gene Technology/Microbiology since 1991. Her major interests are in the development of non-invasive methods to assess oocyte and embryo quality, and regulation of gene expression, spindle formation and cell cycle control at mammalian oogenesis, and in reproductive toxicology and stem cell research.

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      Further studies are required to support this notion. We and others found previously that alterations in the epitope of histone H3 at residues 9 and 10 are associated with spindle aberrations, chromosomal misalignment, and congression failures in mouse MII oocytes (54–56). Accessibility of the epitope recognized by antibody to trimethylated H3 lysine 9 does not appear to be affected by serine 10 phosphorylation status (57).

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    Ursula Eichenlaub-Ritter has been Professor for Cell Biology at the University of Bielefeld, Department of Gene Technology/Microbiology since 1991. Her major interests are in the development of non-invasive methods to assess oocyte and embryo quality, and regulation of gene expression, spindle formation and cell cycle control at mammalian oogenesis, and in reproductive toxicology and stem cell research.

    Preliminary results of the study were presented at the 7th Biennial Conference of ALPHA (Scientists in Reproductive Medicine) in Istanbul, 2008, and at the 24th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Barcelona, 2008.

    Declaration: The authors report no financial or commercial conflicts of interest.

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