Predivision in human oocytes at meiosis I: a mechanism for trisomy formation in man

Angell, Roslyn

doi:10.1007/bf00201839

Cited by 204 publications

(150 citation statements)

References 30 publications

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“…This presumably results from premature predivision of the whole chromosomes into sister chromatids, which then segregate at random. 5 Furthermore, this interpretation is consistent with fluorescence in situ hybridisation (FISH) analyses of aneuploidy for five to eight mainly acrocentric chromosomes in the two by-products of female meiosis, the first (PB1) and second polar bodies (PB2), that is, the majority of errors in PB1 were detected as one or three hybridisation signal(s) for a particular chromosome instead of the normal two. 6,7 The incidence of chromosome aneuploidy in human preimplantation embryos following IVF, particularly in women of advanced maternal age, is high and is assumed to contribute to the rapid decline in pregnancy and live birth rates.…”

Section: Introductionsupporting

confidence: 67%

Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation

Handyside

Montag

Magli³

et al. 2012

Eur J Hum Genet

150

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Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis following natural conception and spontaneous miscarriage demonstrates that trisomies arise mainly in female meiosis and particularly in the first meiotic division. Here, we studied copy number gains and losses for all chromosomes in the two by-products of female meiosis, the first and second polar bodies, and the corresponding zygotes in women of advanced maternal age undergoing IVF, using microarray comparative genomic hybridisation (array CGH). Analysis of the segregation patterns underlying the copy number changes reveals that premature predivision of chromatids rather than non-disjunction of whole chromosomes causes almost all errors in the first meiotic division and unlike natural conception, over half of aneuploidies result from errors in the second meiotic division. Furthermore, most abnormal zygotes had multiple aneuploidies. These differences in the aetiology of aneuploidy in IVF compared with natural conception may indicate a role for ovarian stimulation in perturbing meiosis in ageing oocytes.

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Section: Introductionsupporting

confidence: 67%

Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation

Handyside

Montag

Magli³

et al. 2012

Eur J Hum Genet

150

View full text Add to dashboard Cite

show abstract

“…According to their finding, premature separation of chromatids during meiosis might be the main factor contributing to the formation of oocytes with abnormal chromosomal complements. They have hypothesized that the gradual but constant age-related degradation of cohesins [131] and other factors holding the four chromatids together during metaphase I is the major contributing factor to the age-related decline in female fecundity [132][133][134].…”

Section: Menopausementioning

confidence: 99%

Reproductive ageing in women

Djahanbakhch

Ezzati

Zosmer

2007

The Journal of Pathology

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The traditional view in respect to female reproduction is that the number of oocytes at birth is fixed and continuously declines towards the point when no more oocytes are available after menopause. In this review we briefly discuss the embryonic development of female germ cells and ovarian follicles. The ontogeny of the hypothalamic-pituitary-gonadal axis is then discussed, with a focus on pubertal transition and normal ovulatory menstrual cycles during female adult life. Biochemical markers of menopausal transition are briefly examined. We also examine the effects of age on female fertility, the contribution of chromosomal abnormalities of the oocyte to the observed decline in female fertility with age and the possible biological basis for the occurrence of such abnormalities. Finally, we consider the effects of maternal age on obstetric complications and perinatal outcome. New data that have the potential to revolutionize our understanding of mammalian oogenesis and follicular formation, and of the female reproductive ageing process, are also briefly considered.

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“…In unfertilised oocytes, the major mechanism of trisomy formation was chromatid predivision rather than chromosome nondisjunction of whole bivalents. 42 Although it was suggested that the high incidence of chromatid predivision was because of the in vitro culture of the oocytes, 43 recently the chromatid predivision hypothesis 42 has been confirmed in fresh, noninseminated oocytes. 38 Balanced predivision has not been considered as a form of aneuploidy, 8,38,43 but it should be considered a predisposing factor for aneuploidy.…”

Section: Chromosome and Chromatid Alterationsmentioning

confidence: 99%

Analysis of nine chromosome probes in first polar bodies and metaphase II oocytes for the detection of aneuploidies

et al. 2003

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We used fluorescent in situ hybridisation (FISH) to detect nine chromosomes (1,13,15,16,17,18,21,22 and X) in 89 first Polar Bodies (1PBs), from in vitro matured oocytes discarded from IVF cycles. In 54 1PBs, we also analysed the corresponding oocyte in metaphase II (MII) to confirm the results; the other 35 1PBs were analysed alone as when preimplantation genetic diagnosis using 1PB (PGD-1PB) is performed. The frequency of aneuploid oocytes found was 47.5%; if the risk of aneuploidy for 23 chromosomes is estimated, the percentage rises to 57.2%. Missing chromosomes or chromatids found in 1PBs of 1PB/MII doublets were confirmed by MII results in 74.2%, indicating that only 25.8% of them were artefactual. Abnormalities observed in 1PBs were 55.8% whole-chromosome alterations and 44.2% chromatid anomalies. We observed a balanced predivision of chromatids for all chromosomes analysed. Differences between balanced predivision in 1PB and MII were statistically significant (Po0.0001, v 2 test); the 1PB was most affected. The mean abnormal segregation frequency for each chromosome was 0.89% (range 0.52-1.70%); so, each of the 23 chromosomes of an oocyte has a risk of 0.89% to be involved in aneuploidy. No significant differences were observed regarding age, type of abnormality (chromosome or chromatid alterations) or frequency of aneuploidy. Nine of the 35 patients (25.7%) whose 1PB and MII were studied presented abnormalities (extra chromosomes) that probably originated in early oogenesis. Analysis of 1PBs to select euploid oocytes could help patients of advanced age undergoing in vitro fertilization (IVF) treatment.

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Predivision in human oocytes at meiosis I: a mechanism for trisomy formation in man

Cited by 204 publications

References 30 publications

Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation

Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation

Reproductive ageing in women

Analysis of nine chromosome probes in first polar bodies and metaphase II oocytes for the detection of aneuploidies

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