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

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...

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Bibliographic Details
Published in:Human reproduction (Oxford) 2009-06, Vol.24 (6), p.1313-1321
Main Authors: Ferguson, Kyle A., Leung, Stefanie, Jiang, Dennis, Ma, Sai
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Aneuploidy
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 21
Fluorescent Antibody Technique
Humans
In Situ Hybridization, Fluorescence
Infertility, Male - genetics
Infertility, Male - metabolism
Infertility, Male - physiopathology
Male
male infertility
meiosis
Meiosis - genetics
meiotic recombination
MutL Protein Homolog 1
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Recombination, Genetic
Spermatocytes - physiology
synaptonemal complex
Synaptonemal Complex - metabolism
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Summary: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.
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/dep021