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Hum. Reprod. Advance Access originally published online on April 15, 2008
Human Reproduction 2008 23(6):1263-1270; doi:10.1093/humrep/den112
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Nuclear organization in human sperm: preliminary evidence for altered sex chromosome centromere position in infertile males

K.A. Finch1,2, K.G.L. Fonseka1, A. Abogrein1, D. Ioannou1, A.H. Handyside2, A.R. Thornhill2, N. Hickson1 and D.K. Griffin1,3

1 Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK 2 The London Bridge Fertility, Gynaecology and Genetics Centre, One St Thomas Street, London SE1 9RY, UK

3 Correspondence address. Tel: +44-1227-823022; Fax: +44-1227-763912; E-mail: d.k.griffin{at}kent.ac.uk

BACKGROUND: Many genetic defects with a chromosomal basis affect male reproduction via a range of different mechanisms. Chromosome position is a well-known marker of nuclear organization, and alterations in standard patterns can lead to disease phenotypes such as cancer, laminopathies and epilepsy. It has been demonstrated that normal mammalian sperm adopt a pattern with the centromeres aligning towards the nuclear centre. The purpose of this study was to test the hypothesis that altered chromosome position in the sperm head is associated with male infertility.

METHODS: The average nuclear positions of fluorescence in-situ hybridization signals for three centromeric probes (for chromosomes X, Y and 18) were compared in normoozoospermic men and in men with compromised semen parameters.

RESULTS: In controls, the centromeres of chromosomes X, Y and 18 all occupied a central nuclear location. In infertile men the sex chromosomes appeared more likely to be distributed in a pattern not distinguishable from a random model.

CONCLUSIONS: Our findings cast doubt on the reliability of centromeric probes for aneuploidy screening. The analysis of chromosome position in sperm heads should be further investigated for the screening of infertile men.

Key words: male infertility/sperm/centromere/FISH

Submitted on January 3, 2008; resubmitted on February 28, 2008; accepted on March 13, 2008.


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