title: Reduced chromosome cohesion measured by interkinetochore distance is associated with aneuploidy even in oocytes from young mice.
abstract: It is becoming clear that reduced chromosome cohesion is an important factor in the rise of maternal age-related aneuploidy. This reduction in cohesion has been observed both in human and mouse oocytes, and it can be measured directly by an increase with respect to maternal age in interkinetochore (iKT) distance between a sister chromatid pair. We have observed variations in iKT distance even in oocytes from young mice and wondered if such differences may predispose those oocytes displaying the greatest iKT distances to be becoming aneuploid. Therefore, we used two methods, one pharmacological (Aurora kinase inhibitor) and one genetic (Fzr1 knockout), to raise aneuploidy rates in oocytes from young mice (age, 1-3 mo) and to examine if those oocytes that were aneuploid had greater iKT distances. We observed that for both Aurora kinase inhibition and Fzr1 knockout, iKT distances were significantly greater in those oocytes that became aneuploid compared to those that remained euploid. Based on these results, we propose that individual oocytes undergo loss in chromosomal cohesion at different rates and that the greater this loss, the greater the risk for becoming aneuploid.
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Merriman
authors.forename: Simon I R
authors.initials: SI
authors.lastname: Lane
authors.forename: Janet E
authors.initials: JE
authors.lastname: Holt
authors.forename: Phoebe C
authors.initials: PC
authors.lastname: Jennings
authors.forename: Irene
authors.initials: I
authors.lastname: García-Higuera
authors.forename: Sergio
authors.initials: S
authors.lastname: Moreno
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
authors.forename: Keith T
authors.initials: KT
authors.lastname: Jones
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics; D002478:Cells, Cultured; D002842:Chromatids / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000502:physiology; D002875:Chromosomes / Q000502:physiology* / Q000648:ultrastructure*; D005260:Female; D018386:Kinetochores / Q000648:ultrastructure*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D023421:Models, Animal; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology
chemical_list: C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; C577585:Fzr1 protein, mouse; D047428:Protein Kinase Inhibitors; D011799:Quinazolines