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19 December 2012 Reduced Chromosome Cohesion Measured by Interkinetochore Distance Is Associated with Aneuploidy Even in Oocytes from Young Mice
Julie A. Merriman, Simon I.R. Lane, Janet E. Holt, Phoebe C. Jennings, Irene García-Higuera, Sergio Moreno, Eileen A. McLaughlin, Keith T. Jones
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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.

Julie A. Merriman, Simon I.R. Lane, Janet E. Holt, Phoebe C. Jennings, Irene García-Higuera, Sergio Moreno, Eileen A. McLaughlin, and Keith T. Jones "Reduced Chromosome Cohesion Measured by Interkinetochore Distance Is Associated with Aneuploidy Even in Oocytes from Young Mice," Biology of Reproduction 88(2), (19 December 2012). https://doi.org/10.1095/biolreprod.112.104786
Received: 13 September 2012; Accepted: 1 December 2012; Published: 19 December 2012
KEYWORDS
aneuploidy
cell cycle
meiosis
meiotic maturation
meiotic spindle
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