Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest

Sandra A. Touati, Eulalie Buffin, Damien Cladière, Khaled Hached, Christophe Rachez, Jan M. van Deursen and Katja Wassmann ()
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Sandra A. Touati: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622
Eulalie Buffin: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622
Damien Cladière: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622
Khaled Hached: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622
Christophe Rachez: Departement de Biologie du Développement et Cellules Souches, CNRS URA2578, Unité de Régulation Epigénétique, Institut Pasteur
Jan M. van Deursen: Mayo Clinic College of Medicine
Katja Wassmann: Sorbonne Universités, UPMC Université Paris 06, Institut de Biologie Paris Seine (IBPS), UMR7622

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Mammalian female meiosis is error prone, with rates of meiotic chromosome missegregations strongly increasing towards the end of the reproductive lifespan. A strong reduction of BubR1 has been observed in oocytes of women approaching menopause and in ovaries of aged mice, which led to the hypothesis that a gradual decline of BubR1 contributes to age-related aneuploidization. Here we employ a conditional knockout approach in mouse oocytes to dissect the meiotic roles of BubR1. We show that BubR1 is required for diverse meiotic functions, including persistent spindle assembly checkpoint activity, timing of meiosis I and the establishment of robust kinetochore–microtubule attachments in a meiosis-specific manner, but not prophase I arrest. These data reveal that BubR1 plays a multifaceted role in chromosome segregation during the first meiotic division and suggest that age-related decline of BubR1 is a key determinant of the formation of aneuploid oocytes as women approach menopause.

Date: 2015
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DOI: 10.1038/ncomms7946

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