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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Article number31
Pages (from-to)1-7
Number of pages7
JournalBiology of Reproduction
Volume88
Issue number2
DOIs
Publication statusPublished - 1 Feb 2013
Externally publishedYes

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Aneuploidy
Oocytes
Chromosomes
Aurora Kinases
Maternal Age
Chromatids
Pharmacology

Cite this

Merriman, J. A., Lane, S. I. R., Holt, J. E., Jennings, P. C., García-Higuera, I., Moreno, S., ... Jones, K. T. (2013). Reduced Chromosome Cohesion Measured by Interkinetochore Distance is Associated with Aneuploidy Even in Oocytes from Young Mice. Biology of Reproduction, 88(2), 1-7. [31]. https://doi.org/10.1095/biolreprod.112.104786
Merriman, Julie A. ; Lane, Simon I.R. ; Holt, Janet E. ; Jennings, Phoebe C. ; García-Higuera, Irene ; Moreno, Sergio ; McLaughlin, Eileen A. ; Jones, Keith T. / Reduced Chromosome Cohesion Measured by Interkinetochore Distance is Associated with Aneuploidy Even in Oocytes from Young Mice. In: Biology of Reproduction. 2013 ; Vol. 88, No. 2. pp. 1-7.
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Merriman, JA, Lane, SIR, Holt, JE, Jennings, PC, García-Higuera, I, Moreno, S, McLaughlin, EA & Jones, KT 2013, 'Reduced Chromosome Cohesion Measured by Interkinetochore Distance is Associated with Aneuploidy Even in Oocytes from Young Mice', Biology of Reproduction, vol. 88, no. 2, 31, pp. 1-7. https://doi.org/10.1095/biolreprod.112.104786

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

In: Biology of Reproduction, Vol. 88, No. 2, 31, 01.02.2013, p. 1-7.

Research output: Contribution to journalArticle

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AU - Lane, Simon I.R.

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AU - Jennings, Phoebe C.

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AB - 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.

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