title: Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors.
abstract: Segregation of homologs at the first meiotic division (MI) is facilitated by crossovers and by a physical constraint imposed on sister kinetochores that facilitates monopolar attachment to the MI spindle. Recombination failure or premature separation of homologs results in univalent chromosomes at MI, and univalents constrained to form monopolar attachments should be inherently unstable and trigger the spindle assembly checkpoint (SAC). Although univalents trigger cell-cycle arrest in the male, this is not the case in mammalian oocytes. Because the spindle assembly portion of the SAC appears to function normally, two hypotheses have been proposed to explain the lack of response to univalents: (1) reduced stringency of the oocyte SAC to aberrant chromosome behavior, and (2) the ability of univalents to satisfy the SAC by forming bipolar attachments. The present study of Mlh1 mutant mice demonstrates that metaphase alignment is not a prerequisite for anaphase onset and provides strong evidence that MI spindle stabilization and anaphase onset require stable bipolar attachment of a critical mass--but not all--of chromosomes. We postulate that subtle differences in SAC-mediated control make the human oocyte inherently error prone and contribute to the age-related increase in aneuploidy.
authors.affiliation: School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99163, USA.
authors.forename: So Iha
authors.initials: SI
authors.lastname: Nagaoka
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hodges
authors.forename: David F
authors.initials: DF
authors.lastname: Albertini
authors.forename: Patricia Ann
authors.initials: PA
authors.lastname: Hunt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D002453:Cell Cycle; D016922:Cellular Senescence; D020090:Chromosome Segregation; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D008809:Mice, Inbred C3H; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism; D012727:Sex Characteristics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1