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

Robles, Pedro; Roig, Ignasi; Garcia, Roberto Brandão; Ortega, Arantxa; Egozcue, J.; Cabero, L.; Garcı́a, M.

doi:10.1530/rep-06-0243

Cited by 18 publications

(15 citation statements)

References 48 publications

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“…Further information on patterns of 21q recombination would be valuable, using analysis of MLH1 recombination foci along the length of the meiosis-specific chromosome pairing structure, the synaptonemal complex at the pachytene stage (Baker et al 1996, Barlow & Hultén 1998, Tease & Hultén 2004, Lenzi et al 2005, Robles et al 2007). The normal positioning of a single MLH1 recombination focus in the middle of 21q is illustrated in Fig.…”

Section: Additional Complexity In Interpreting Results and Further Stmentioning

confidence: 99%

On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model

Hultén

Patel²,

Jonasson³

et al. 2010

Reproduction

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We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. In particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent largescale studies in families, tracing DNA markers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women.

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Section: Additional Complexity In Interpreting Results and Further Stmentioning

confidence: 99%

On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model

Hultén

Patel²,

Jonasson³

et al. 2010

Reproduction

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“…This is based upon FISH analysis of cells in prophase from second-trimester female fetuses [Cheng et al, 1998;Robles et al, 2007;Rowsey et al, 2013]. However, evidence from informative studies on oocytes suggests that it may affect 10-20% of oocytes from the population of women undergoing in vitro fertilisation (IVF) for a variety of reasons [Mahmood et al, 2000;Pujol et al, 2003;Obradors et al, 2010;Ghevaria et al, 2013].…”

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confidence: 99%

The Contribution of Germinal Mosaicism to Human Aneuploidy

Ghevaria

SenGupta

Sarna

et al. 2014

Cytogenet Genome Res

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Germinal mosaicism in a parent is considered to be a rare cause of aneuploidy in the offspring. The aim of this study was to assess the incidence of pre-meiotic errors, indicative of germinal mosaicism, leading to aneuploidy compared with those that occur at meiosis I. The material consisted of 126 oocytes, unexposed to sperm, donated by 57 women with an average maternal age of 35. The oocytes were at various stages of maturity and were analysed by array comparative genomic hybridisation. Of these, 102 gave conclusive results, comprising 47 that were immature, at the germinal vesicle (GV) or metaphase I stage (MI); 34 complete metaphase II-first polar body (MII-PB) complexes together with 21 incomplete complexes. Oocytes at the GV or MI stage provide direct evidence of pre-meiotic aneuploidy. Complete MII-PB complexes with the expected reciprocal gains/losses provide information on MI errors; those with non-reciprocal gains have pre-meiotic errors. Overall, 29 oocytes were aneuploid, and the source of the error was known for 21. In 8 (from 7 women) the error was pre-meiotic consisting of 4 MI oocytes and 4 MII-PB complexes with non-reciprocal gains. The remaining 13 were the result of errors at meiosis I. Although pre-meiotic errors occurred in only 10% of informative oocytes, most notable was the fact that for those oocytes where the source of the error was known, 38% were caused by germinal mosaicism compared with 62% that were the outcome of a meiosis I error. None of the women with germinal mosaicism were infertile.

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“…On the other hand, they could have originated during the proliferative phase of oogenesis, and maintained in the ovaries due to errors in oogenesis checkpoint mechanisms that should derive them to atresia. [26][27][28][29] Hormonal treatment has also been proposed as a triggering agent in aneuploidy recruitment in different groups of women. A preferential recovery of the aneuploid oocytes with more aneuploid events, which originated from aneuploid oogonia, was found in young females as a possible effect of intensive hormonal stimulation.…”

Section: Oocyte Aneuploidymentioning

confidence: 99%

Non-meiotic chromosome instability in human immature oocytes

et al. 2013

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Aneuploidy has been a major issue in human gametes and is closely related to fertility problems, as it is known to be present in cleavage stage embryos and gestational losses. Pre-meiotic chromosome abnormalities in women have been previously described. The aim of this study is to assess the whole-chromosome complement in immature oocytes to find those abnormalities caused by mitotic instability. For this purpose, a total of 157 oocytes at the germinal vesicle or metaphase I stage, and discarded from IVF cycles, were analysed by CGH. Fifty-six women, between 18 and 45 years old (mean 32.5 years), including 32 IVF patients (25-45 years of age) and 24 IVF oocyte donors (18-33 years of age), were included in the study. A total of 25/157 (15.9%) of the oocytes analysed, obtained from three IVF clinics, contained chromosome abnormalities, including both aneuploidy (24/157) and structural aberrations (9/157). Independently of the maternal age, the incidence of abnormal oocytes which originated before meiosis is 15.9%, and these imbalances were found in 33.9% of the females studied. This work sheds light on the relevance of mitotic instability responsible for the generation of the abnormalities present in human oocytes. European Journal of Human Genetics ( Keywords: premeiotic instability; immature oocytes; aneuploidy; segmental imbalances; germline mitotic abnormalities INTRODUCTION Aneuploidy has been a major issue in human gametes, and is highly related to fertility problems. It is known to be present in cleavage stage embryos and gestational losses. 1,2 The prevailing mechanism causing aneuploidy in humans concerns maternal meiotic mal-segregation. Several studies have focused their interest on oocyte aneuploidy, mainly those which originate during the first and second meiotic divisions. 1 For this purpose, first and second polar bodies (1PB and 2PB) and the corresponding metaphase II (MII) oocytes have been analysed, describing aneuploidies of meiotic origin, mainly caused by chromosome non-disjunction and/ or sister chromatid predivision. 3 Meiotic studies have been performed in oocytes using a great variety of cytogenetic methodologies. R-banding karyotyping on 1397 oocytes showed aneuploidies in 10.8% of the cells studied. 4 An aneuploidy rate of 47.5% was observed when 1PB-MII oocyte doublets were analysed by 9-chr FISH. 5 In studies where the wholechromosome complement was assessed by spectral karyotyping, aneuploidy rates from 16.7% (10/60) 6 to 42.5% (20/47) 7 were detected. Using comparative genomic hybridisation (CGH), a great variability of aneuploidy rates was found, when different wholegenome amplification methodologies were used to amplify the DNA from single cells, and aneuploidy rates found in 1PB-MII oocyte doublets varied from 3% in oocyte donors 8 to 65% in IVF patients. 9

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

Cited by 18 publications

References 48 publications

On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model

On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model

The Contribution of Germinal Mosaicism to Human Aneuploidy

Non-meiotic chromosome instability in human immature oocytes

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