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.