Chromosome segregation in mammalian oocytes is prone to errors causing aneuploidy with consequences such as precocious termination of development or severe developmental disorders. Aneuploidy also represents a serious problem in procedures utilizing mammalian gametes and early embryos in vitro. In our study, we focused on congression defects during meiosis I and observed whole nondisjoined bivalents in meiosis II as a direct consequence, together with a substantially delayed first polar body extrusion. We also show that the congression defects are accompanied by less stable attachments of the kinetochores. Our results describe a process by which congression defects directly contribute to aneuploidy.

1.
Chiang T, Duncan FE, Schindler K, Schultz RM, Lampson MA: Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol 20:1522-1528 (2010).
2.
Chmátal L, Gabriel SI, Mitsainas GP, Martínez-Vargas J, Ventura J, et al: Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice. Curr Biol 24:2295-2300 (2014).
3.
Chmátal L, Yang K, Schultz RM, Lampson MA: Spatial regulation of kinetochore microtubule attachments by destabilization at spindle poles in meiosis I. Curr Biol 25:1835-1841 (2015).
4.
Collins J, Jones KT: DNA damage responses in mammalian oocytes. Reproduction 152:R15-R22 (2016).
5.
Danadova J, Matijescukova N, Danylevska AM, Anger M: Increased frequency of chromosome congression defects and aneuploidy in mouse oocytes cultured at lower temperature. Reprod Fertil Dev DOI: 10.1071/RD1530 (2016).
6.
Eichenlaub-Ritter U: Oocyte ageing and its cellular basis. Int J Dev Biol 56:841-852 (2012).
7.
Hassold T, Hunt P: To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2:280-291 (2001).
8.
Herbert M, Kalleas D, Cooney D, Lamb M, Lister L: Meiosis and maternal aging: insights from aneuploid oocytes and trisomy births. Cold Spring Harb Perspect Biol 7:a017970 (2015).
9.
Holt JE, Lane SI, Jennings P, García-Higuera I, Moreno S, Jones KT: APC (FZR1) prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing. Mol Biol Cell 23:3970-3981 (2012).
10.
Hornak M, Jeseta M, Musilova P, Pavlok A, Kubelka M, et al: Frequency of aneuploidy related to age in porcine oocytes. PLoS One 6:e18892 (2011).
11.
Ishiguro T, Tanaka K, Sakuno T, Watanabe Y: Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase. Nat Cell Biol 12:500-506 (2010).
12.
Jones KT, Lane SI: Molecular causes of aneuploidy in mammalian eggs. Development 140:3719-3730 (2013).
13.
Katis VL, Lipp JJ, Imre R, Bogdanova A, Okaz E, et al: Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Dev Cell 18:397-409 (2010).
14.
Kovacovicova K, Awadova T, Mikel P, Anger M: In vitro maturation of mouse oocytes increases the level of Kif11/Eg5 on meiosis II spindles. Biol Reprod 95:18 (2016).
15.
Kudo NR, Wassmann K, Anger M, Schuh M, Wirth KG, et al: Resolution of chiasmata in oocytes requires separase-mediated proteolysis. Cell 126:135-146 (2006).
16.
Kudo NR, Anger M, Peters AH, Stemmann O, Theussl HC, et al: Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. J Cell Sci 122:2686-2698 (2009).
17.
Lane SI, Yun Y, Jones KT: Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension. Development 139:1947-1955 (2012).
18.
Lister LM, Kouznetsova A, Hyslop LA, Kalleas D, Pace SL, et al: Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2. Curr Biol 20:1511-1521 (2010).
19.
Mailhes JB: Faulty spindle checkpoint and cohesion protein activities predispose oocytes to premature chromosome separation and aneuploidy. Environ Mol Mutagen 49:642-658 (2008).
20.
Nagaoka SI, Hassold TJ, Hunt PA: Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet 13:493-504 (2012).
21.
Petronczki M, Siomos MF, Nasmyth K: Un ménage à quatre: the molecular biology of chromosome segregation in meiosis. Cell 112:423-440 (2003).
22.
Phadnis N, Cipak L, Polakova S, Hyppa RW, Cipakova I, et al: Casein kinase 1 and phosphorylation of cohesin subunit Rec11 (SA3) promote meiotic recombination through linear element formation. PLoS Genet 11: e1005225 (2015).
23.
Revenkova E, Herrmann K, Adelfalk C, Jessberger R: Oocyte cohesin expression restricted to predictyate stages provides full fertility and prevents aneuploidy. Curr Biol 20:1529-1533 (2010).
24.
Rumpf C, Cipak L, Dudas A, Benko Z, Pozgajova M, et al: Casein kinase 1 is required for efficient removal of Rec8 during meiosis I. Cell Cycle 9:2657-2662 (2010).
25.
Sebestova J, Danylevska A, Novakova L, Kubelka M, Anger M: Lack of response to unaligned chromosomes in mammalian female gametes. Cell Cycle 11:3011-3018 (2012).
26.
Simunić J, Tolić IM: Mitotic spindle assembly: building the bridge between sister K-fibers. Trends Biochem Sci 41:824-833 (2016).
27.
Tachibana-Konwalski K, Godwin J, van der Weyden L, Champion L, Kudo NR, et al: Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes Dev 24:2505-2516 (2010).
28.
Touati SA, Wassmann K: How oocytes try to get it right: spindle checkpoint control in meiosis. Chromosoma 125:321-335 (2015).
29.
Tsutsumi M, Fujiwara R, Nishizawa H, Ito M, Kogo H, et al: Age-related decrease of meiotic cohesins in human oocytes. PLoS One 9:e96710 (2014).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.