Meiotic non-disjunction mechanisms in human fertile males.

BACKGROUND In humans, little is known about the mechanisms of non-disjunction working in male meiosis, although considerable attention has been given to these mechanisms in female meiosis. The present study explores the origin of meiotic non-disjunction during human spermatogenesis and the chromosomes most commonly involved in this process. METHODS We used Multiplex fluorescence in situ hybridization to carry out meiotic analyses in metaphase I (MI) and metaphase II (MII) spermatocytes from three fertile donors. Testicular biopsy was obtained during a vasectomy procedure. RESULTS We examined a total of 317 MI and 248 MII spermatocytes. The frequency of numerical chromosome abnormalities at MII (14.5%) was 5.5 times higher than at MI (2.5%). We observed 88 (27.7%) spermatocytes I with chromosome bivalents with a low chiasma count, usually small chromosomes displaying two separated univalents. Chromosomes X, Y and 21 were the most commonly found as achiasmate chromosomes at MI and the most frequently involved in disomy at MII. Hyperploidy frequency in spermatocytes II (disomy) was significantly higher (P< 0.001) than that found in spermatocytes I (trisomy). CONCLUSIONS Achiasmate non-disjunction and premature separation of sister chromatids appear to be the two main non-disjunction mechanisms during the first meiotic division in human spermatogenesis, and both mechanisms contribute equally to the genesis of aneuploidy. The elevated frequencies of disomy detected in spermatocytes II are significantly higher than those previously described in human spermatozoa, suggesting the existence of a postmeiotic checkpoint monitoring numerical abnormalities.