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Hum. Reprod. Advance Access originally published online on February 25, 2009
Human Reproduction 2009 24(6):1313-1321; doi:10.1093/humrep/dep021
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© The Author 2009. 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

Distribution of MLH1 foci and inter-focal distances in spermatocytes of infertile men

Kyle A. Ferguson, Stefanie Leung, Dennis Jiang and Sai Ma1

Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada

1 Correspondence address. Department of Obstetrics and Gynaecology, Room D414B, BC Women's Hospital and Health Centre, D6-4500 Oak Street, Vancouver, British Columbia, Canada V6H 3N1. Tel: +1 604-875-2345 ext: 5686; Fax: +1 604-875-2722; Email: sai{at}interchange.ubc.ca

BACKGROUND: In a previous study on severely infertile men, we observed alterations in the number of meiotic crossovers; however, it is unknown if these men also show alterations in the position of crossovers.

METHODS: Spermatocytes from 15 men (5 control men and 10 infertile men) were immunostained to observe the synaptonemal complex and MLH1 foci, which localize to sites of crossovers. Fluorescent in situ hybridization was performed to identify chromosomes 13, 18 and 21. Chromosome bivalents were separated into those with single and double crossover configurations, and the distribution of MLH1 foci along each chromosome arm was calculated. The inter-focal distances on chromosome 13 and 18 bivalents with double crossovers were also calculated.

RESULTS: Four of the infertile men displayed an altered MLH1 distribution on at least one of the chromosome arms studied. Of these four men, two displayed reduced rates of meiotic recombination. Only one man displayed an abnormality in crossover interference, with inter-focal distances reduced on chromosome 13 bivalents.

CONCLUSIONS: Recombination defects in infertile men may include alterations in the number of crossovers, the position of crossovers or both. Alterations in both the number and position of crossovers may increase the risk of aneuploid sperm in infertile men.

Key words: male infertility/meiosis/meiotic recombination/synaptonemal complex/aneuploidy

Submitted on May 1, 2008; resubmitted on January 10, 2009; accepted on January 15, 2009.


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