title: Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin.
abstract: Mouse oocytes lack canonical centrosomes and instead contain unique acentriolar microtubule-organizing centers (aMTOCs). To test the function of these distinct aMTOCs in meiotic spindle formation, pericentrin (Pcnt), an essential centrosome/MTOC protein, was knocked down exclusively in oocytes by using a transgenic RNAi approach. Here, we provide evidence that disruption of aMTOC function in oocytes promotes spindle instability and severe meiotic errors that lead to pronounced female subfertility. Pcnt-depleted oocytes from transgenic (Tg) mice were ovulated at the metaphase-II stage, but show significant chromosome misalignment, aneuploidy and premature sister chromatid separation. These defects were associated with loss of key Pcnt-interacting proteins (γ-tubulin, Nedd1 and Cep215) from meiotic spindle poles, altered spindle structure and chromosome-microtubule attachment errors. Live-cell imaging revealed disruptions in the dynamics of spindle assembly and organization, together with chromosome attachment and congression defects. Notably, spindle formation was dependent on Ran GTPase activity in Pcnt-deficient oocytes. Our findings establish that meiotic division is highly error-prone in the absence of Pcnt and disrupted aMTOCs, similar to what reportedly occurs in human oocytes. Moreover, these data underscore crucial differences between MTOC-dependent and -independent meiotic spindle assembly.
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Claudia
authors.identifier: 0000-0002-4647-0839
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Luhan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA viveiros@uga.edu.|Regenerative Biosciences Center (RBC), University of Georgia, Athens, GA 30602, USA.
authors.forename: Maria M
authors.identifier: 0000-0001-9526-8410
authors.initials: MM
authors.lastname: Viveiros
mesh_terms: D000782:Aneuploidy; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002470:Cell Survival; D033481:Chromosomes, Mammalian / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D021621:Imaging, Three-Dimensional; D007246:Infertility / Q000378:metabolism* / Q000473:pathology*; D008540:Meiosis; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism* / Q000473:pathology*; D064048:Spindle Pole Bodies / Q000378:metabolism; D020931:ran GTP-Binding Protein
chemical_list: D000941:Antigens; C086178:pericentrin; D020931:ran GTP-Binding Protein
keywords: MTOC; Meiosis; Microtubule-organizing center; Oocyte; Pericentrin; Spindle