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

Abstract

Little is known about the first meiotic prophase stages in the human female because these occur during fetal life, and only a few studies have addressed aneuploid human oocytes. In this paper, the synaptic process in the meiotic prophase in three 47, XX 1 18 cases is analyzed. A complete study of the dynamics of centromeres and telomeres, cohesin core and synapsis development in aneuploid female meiosis was performed. Investigation of chromosome dynamics in prophase of trisomy 18 oocytes show that these events follow the major patterns seen earlier in euploid oocytes. However, there is a significant delay in the resolution of bouquet topology which could relate to the presence of a surplus chromosome 18 axial element in zygotene oocytes. Pachytene oocytes displayed normal synapsis among the three chromosome 18s. However, in some oocytes the surplus chromosome 18 core was aligned to the bivalent 18. As ataxia telangiectasia and Rad3 related kinase (ATR) has been described as a marker for late-pairing chromosomes in mice, ATR distribution was analyzed in human meiocytesspermatocytes, euploid oocytes and trisomic oocytes. In contrast to the observations made in mice, no preferential staining for late-pairing chromosomes was observed in humans. In the cases studied, bivalent synapses progressed as in a normal ovary, contrasting with the hypothesis that a surplus chromosome can modify pairing of other chromosomes.

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

“…The age of each case was calculated from the last menstrual period and echogram. The results presented in this paper are based on 12 samples that, all of them, were used for the first time in this study, and sample V94 was used in a previous study with different goals (Table 1; Roig et al 2005b). Nevertheless, in order to deepen the knowledge of the pairing and synaptic processes, our results obtained in this study were compared with previously published data (Roig et al 2004(Roig et al , 2005a(Roig et al , 2005b.…”

“…Samples were also processed to obtain structurally preserved nuclei preparations (Roig et al 2004), which enabled a 3D study of the nucleus, and oocyte spreads for IF and FISH purposes, as described recently (Martínez-Flores et al 2003, Roig et al 2004, 2005b, were used to characterize homologue chromosome pairing and synapsis in detail.…”

“…In order to study the homologue chromosome 21, 13, and X pairing processes, FISH was performed in euploid and aneuploid methanol:acetic acid spread oocytes as described previously (Roig et al 2005b). Different commercial (Vysis, Downers Grove, IL, USA, and Cambio, Cambridge, UK) and non-commercial (provided by Dr R Stanyon, National Cancer Institute-Frederick, Frederick, MD, USA) WCP, as well as a 13q14/21q22 locus-specific identification (LSI) probe (Oncor, Gaithersburg, MD, USA), were used.…”

“…Fluorescence in situ hybridization (FISH) has enabled the analysis of particular homologue pairing processes of euploid and aneuploid oocytes using whole chromosome probes (WCP) alone or combined with locus identification probes (Cheng & Gartler 1994, Cheng et al 1995, 1998, Cheng & NaluaiCecchini 2004, Roig et al 2005a or particular sets of probes to study oocytes with rearranged genomes (Cheng et al 1999, Cheng & Naluai-Cecchini 2004. More recently, studies have used immunofluorescence (IF) to primarily analyze meiotic recombination (Barlow & Hultén 1997, Hartshorne et al 1999, Roig et al 2004, 2005b, Lenzi et al 2005. In most of these studies, important differences concerning homologue synapsis and the recombination progression process between male and female meiosis are described both in humans (Bojko 1983, Rasmussen & Holm 1984, Roig et al 2004, Lenzi et al 2005, Oliver-Bonet et al 2005) and mice (Morelli & Cohen 2005), suggesting that these may be involved in the differences observed in the origin of human aneuploidy.…”

“…Because most of the recent studies performed in mammalian meiosis have focused on studying meiotic recombination, only little is known about the homologue pairing process and synapsis, and this is also true for human oocytes , Cheng & Naluai-Cecchini 2004, Roig et al 2004, 2005a, 2005b, Lenzi et al 2005. On the other hand, chromosomes 13, 21, and X are involved in some of the most common human trisomies, and in the aneuploidies shown by oocytes at metaphase II (Cupisti et al 2003, Pujol et al 2003.…”