title: Loss of Centromere Cohesion in Aneuploid Human Oocytes Correlates with Decreased Kinetochore Localization of the Sac Proteins Bub1 and Bubr1.
abstract: In human eggs, aneuploidy increases with age and can result in infertility and genetic diseases. Studies in mouse oocytes suggest that reduced centromere cohesion and spindle assembly checkpoint (SAC) activity could be at the origin of chromosome missegregation. Little is known about these two features in humans. Here, we show that in human eggs, inter-kinetochore distances of bivalent chromosomes strongly increase with age. This results in the formation of univalent chromosomes during metaphase I (MI) and of single chromatids in metaphase II (MII). We also investigated SAC activity by checking the localization of BUB1 and BUBR1. We found that they localize at the kinetochore with a similar temporal timing than in mitotic cells and in a MPS1-dependent manner, suggesting that the SAC signalling pathway is active in human oocytes. Moreover, our data also suggest that this checkpoint is inactivated when centromere cohesion is lost in MI and consequently cannot inhibit premature sister chromatid separation. Finally, we show that the kinetochore localization of BUB1 and BUBR1 decreases with the age of the oocyte donors. This could contribute to oocyte aneuploidy.
authors.affiliation: Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.|Unité de Cytogénétique DPI, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lagirand-Cantaloube
authors.affiliation: Unité de Cytogénétique DPI, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Ciabrini
authors.affiliation: Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Charrasse
authors.affiliation: Unité d'AMP DPI, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Ferrieres
authors.affiliation: Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Castro
authors.affiliation: Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.|Unité de Cytogénétique DPI, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France.|Département de Gynécologie Obstétrique, Equipe Médecine de la Reproduction, CHU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France.
authors.forename: Tal
authors.initials: T
authors.lastname: Anahory
authors.affiliation: Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, CNRS UMR 5237, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lorca
mesh_terms: D000782:Aneuploidy; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport
chemical_list: C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases