Meiotic non-disjunction mechanisms in human fertile males

Abstract

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.

Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest

“…48). Trisomy 21 pregnancies (95%) are due to errors in female meiosis 48 , whereas errors in chromosome segregation in male meiosis are much lower, being around 2.5% for autosomes 49 . Unlike meiotic divisions in males, which take place immediately after pachytene and successful recombination, female meiosis comes to a halt for weeks or months (in mice) or decades (in humans) in prophase I, before meiosis is resumed to give rise to one or more fertilizable eggs.…”

Sperm FISH and chromatin integrity in spermatozoa from a t(6;10;11) carrier

“…Our results indicated such a frequency at 2.31%, while three other cases of three-way CCR analyses found it to be 9.3% (Loup et al 2010), 3.15% (Pellestor et al 2011b) and 15.6% (Godo et al 2013). Unexpected FISH phenotypes can be the consequence of three factors: i) nondisjunction at the second meiotic division, ii) increasing difficulty in FISH result interpretation with increasing number of chromosomes involved, and iii) possible chiasma occurrence, leading to the formation of additional recombinant chromosomes (Anton et al 2007, Uroz & Templado 2012. In cases of three-way der (6) der (10) 10 6 11 der (11) q25.1 q24.3 q23.1 Figure 3 Schematic model of the suggested hexavalent configuration during the pachytene stage in meiosis I in a 46,XY,t(6;10;11)(q25.1;q24.3;q23.1)mat carrier.…”

Sperm aneuploidy in infertile male patients: a systematic review of the literature

“…Studies conducted to date have shown that the overall disomy frequencies observed in spermatocytes II are significantly higher than those observed in mature human spermatozoa, suggesting the existence of effective, post‐meiotic checkpoint mechanisms that monitor and arrest spermatocytes II with numerical abnormalities. Inefficient control mechanisms could, therefore, be one explanation for the increased rate of chromosome abnormalities observed in the spermatozoa of certain male subgroups (Uroz & Templado, ).…”