Reduced recombination associated with the production of aneuploid sperm in an infertile man : a case report

Studies using gene-linkage analysis have suggested that abnormal recombination during meiosis may lead to the production of aneuploid gametes; however, there is little direct evidence of a link between the two in human males. We analysed spermatocytes in the pachytene stage from a man with extremely high aneuploidy rates in his sperm. Testicular tissue specimens of the infertile man and two vasectomy reversals were processed with immuofluorescent techniques to visualize synaptonemal complex and recombination foci and fluorescent in situ hybridization on spermatocytes and sperm with probes for chromosomes 13, 21, 18, X and Y. We observed no recombination between sex chromosomes in the infertile man, while in two controls, we observed recombination rates of 79.3 and 81.0% between the sex chromosomes. This was associated with a total sex aneuploidy rate of 41.61 % in testicular sperm of the infertile man (0.44 and 0.62% in two controls). Recombination on chromosome 21 was reduced in the infertile man, with 10.62% of spermatocytes showing no recombination (0 and 1.67% in two controls), as well as chromosome 13, with 53.98% having ≤1 recombination foci (22.05 and 21.67% in two controls). This was associated with increased aneuploidy for those chromosomes. Chromosome 18 aneuploidy was slightly increased, although there was no apparent decrease in recombination. These results provide the first evidence of both recombination and non-disjunction abnormalities in the same individual. This is also the only reported case of an infertile man who shows no recombination between the sex chromosomes, despite the formation of the sex body.