Meiotic chromosome pairing in fetal oocytes of trisomy 21 human females

Abstract

The influence of trisomy on meiotic chromosome association and synapsis was studied in oocytes of two trisomy 21 fetuses. The patterns of association of the three chromosomes 21 were determined by analysis of late zygotene to early diplotene fetal oocytes after immunofluorescent staining of synaptonemal complexes. The identity of chromosome 21 was confirmed using FISH with either a whole chromosome 21 paint or an α-satellite DNA repeat probe. In both fetuses, a wide variety of configurations was present at pachytene. The most common configurations were a trivalent (35.5% and 51.6% of analyzable cells) and a bivalent plus univalent (62.9% and 45.2%). These different frequencies between the fetuses were not significant. Trivalents showed either triple synapsis or double synapsis with pairing-partner switches. The extent of triple synapsis varied from a short segment, either terminal or interstitial, to the whole chromosome length. Through use of immunofluorescent staining of the centromeres, we identified novel types of abnormal chromosome behavior in trisomy 21 fetal oocytes. Thus, we found that 6/41 trivalents had one of the chromosomes associated “out of register,” i.e., in a nonhomologous fashion, with its two homologs. Likewise, we found three cells with bivalent plus univalent configurations, in which the univalent showed self-synapsis. The presence of three copies of chromosome 21 therefore results not only in the formation of complex and highly variable synaptic associations but also causes a significant increase in the occurrence of nonhomologous synapsis in human fetal oocytes.

Pairing and synapsis in oocytes from female fetuses with euploid and aneuploid chromosome complements

“…Alternatively, as proposed recently (Borner et al 2004), crossover designation is established early in meiotic prophase when homologues start pairing; thus, we believe, in the case of the trisomic 21 oocytes, the three homologue 21s may contact only two by two; therefore, two crossovers are designated for trivalent 21. Nonhomologous synapsis has been reported to occur in trisomic 21 oocytes (Barlow et al 2002). Nevertheless, we have not observed any indication of this happening in our samples.…”

“…Moreover, in this study, the number of oocytes analyzed is significantly higher than those reported in the other studies. Secondly, a high variability between samples concerning synaptic configurations achieved by the three chromosome 21s has been observed in previous studies (Barlow et al 2002) and here (data not shown). This fact would be in agreement with other studies focused in the recombination process, suggesting the existence of a high variability between samples in humans (Lenzi et al 2005).…”

Chromosome 18 pairing behavior in human trisomic oocytes. Presence of an extra chromosome extends bouquet stage

“…This phenomenon is not restricted to humans, and has also been observed in rat meiocytes (Martínez-Flores et al 2001). However, recent studies in which IF techniques have been applied to stain SYCP3 in human trisomic 21 oocytes have not observed any univalent thickening, suggesting that SYCP3 is not implicated in this phenomenon (Barlow et al 2002).…”

“…Nevertheless, in all cases, at least two homologs seem to pair normally forming a bivalent, and even pairing of the three homologs (trivalent formation) has been described in all studied cases, with different efficiency (Luciani et al 1976, Wallace & Hulten 1983, Speed 1984, Cheng et al 1995, Barlow et al 2002. In some of these papers a disturbing effect of the extra chromosome on the pairing process of other homologs is suggested (Cheng et al 1998).…”

“…The meiotic division is blocked until the female enters puberty. Despite the difficulties associated with the study of human female meiotic prophase, some aneuploid ovaries have been studied using classical staining techniques (Luciani et al 1976, Wallace & Hulten 1983, Speed 1984, fluorescent in situ hybridization (FISH) (Cheng et al 1995(Cheng et al , 1998 or immunofluorescent (IF) (Barlow et al 2002) techniques.…”