Errors at mitotic segregation early in oogenesis and at first meiotic division in oocytes from donor females: Comparative genomic hybridization analyses in metaphase II oocytes and their first polar body

Obradors, Albert; Rius, Mariona; Cuzzi, Juliana; Daina, Gemma; Gutiérrez-Mateo, Cristina; Pujol, Aïda; Marina, Fernando; Márquez, Carmen; Benet, Jordi; Navarro, J.

doi:10.1016/j.fertnstert.2009.08.050

Cited by 26 publications

(28 citation statements)

References 34 publications

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“…12 Afterwards, subsequent studies analysing 1PB and MII oocyte doublets by CGH also showed non-complementary results, with heterogeneous incidence, attributable to the existence of precursor aneuploid oogonia not only in IVF patients, but also in oocyte donors, as shown in Table 3. 8,[13][14][15][16][17][18] The overall aneuploidy rate detected was similar to that previously described in oocyte donors (younger than 29 years of age) and a bit higher than that previously identified in IVF patients (21-42 years of age) ( Table 3). The differences observed could be attributable to the size of the samples and the variability among the patients included in each study.…”

Section: Oocyte Aneuploidysupporting

confidence: 87%

“…The mechanism responsible for aneuploidies reported here had been previously described in 25.7% of the females when analysing MII-1PB doublets from IVM oocytes using 9-chr FISH. 5 The incidence observed in the present work is higher than the 13.2% found in IVF patients of 21-42 years of age [13][14][15] and in 22.6% of IVF oocytes from donorso29 years of age, 18 where the wholechromosome complement of mature oocytes (1PB-MII doublets) was evaluated.…”

Section: Segmental Imbalancescontrasting

confidence: 48%

“…Contrary to previously published results of analysing oocytes from IVF donors, mitotic errors displayed more than one altered chromosome, while meiotic errors involved single chromosomes only. 18 Aneuploidy origin As stated above, no differences have been observed regarding the aneuploidy rate in immature oocytes depending on maternal age. Accordingly, it can be inferred that the mechanism responsible for this type of events produced during embryonic development would be present in a basal level in all women, having an individual-dependent prevalence rather than being related to maternal age.…”

Section: Oocyte Aneuploidymentioning

confidence: 90%

“…Non-complementary rates between 1 and 15.5% have been described. 8,[13][14][15][16][17][18] It has been postulated that these aneuploid cells could have originated in the early mitotic divisions of the embryo or during mitotic proliferation of the oogonia in embryogenesis. 19,20 Additionally, direct studies in ovaries of euploid fetuses indicate that ovary mosaicism might be a common situation.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Oocyte Aneuploidysupporting

confidence: 87%

Section: Segmental Imbalancescontrasting

confidence: 48%

Section: Oocyte Aneuploidymentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Non-meiotic chromosome instability in human immature oocytes

et al. 2013

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“…During this time, Oocyte accumulates large members of mRNA transcripts and proteins. These raw materials implement basic biosynthetic processes in the early embryo, direct the first mitotic divisions, and support early embryonic development [4]. It is reasonable to assume that some oocytes may acquire different amounts of transcripts and proteins that, in turn, affect chromosome stability [5].…”

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confidence: 99%

Age-related increase in aneuploidy and alteration of gene expression in mouse first polar bodies

Jiao

Woodruff

2014

J Assist Reprod Genet

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Purpose To confirm that aneuploidy candidate genes are detectable in the first polar body (PB 1 ) of MII oocytes and to investigate the age-dependent molecular changes in PB 1 . Methods Aged (12-to 15-mo-old) and young (2-mo-old) mice were administered pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotrophin (hCG). MII oocytes were obtained and the first PB was removed. mRNA from each PB and its sibling oocyte was reverse transcribed. Real-time PCR was performed to quantify the expression of six genes (BUB1, CDC20, Filia, MCAK, SGOL1, SMC1A) in single PB. Results We first demonstrated that detection and quantification of transcripts associated with aneuploidy in single mouse oocyte and sibling PB 1 is possible and the relative abundance of mRNA transcripts in a single PB faithfully reflects the relative abundance of that transcript in its sibling oocyte. We further found that transcript levels were significantly lower in aged PBs compared with young PBs (P<0.05). Conclusions Our results suggest that the detection and analysis of polar body mRNA may provide insight in age-related aneuploidy in oocyte. This analysis is a novel concept to investigate the genesis of chromosome abnormality and could potentially assist in the characterization of mechanisms underlying key molecular origin of female meiotic aneuploidy, which would be of great scientific and clinical value.

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Origins of Human Aneuploidy

Delhanty¹

2018

Encyclopedia of Life Sciences

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At birth, at least 1% of humans have a clinically significant chromosomal abnormality. However, this represents a small fraction of those originally conceived as by the time of birth, natural selection has eliminated the vast majority of abnormal embryos and foetuses. There are three stages in development when aneuploidy may arise: during gamete formation, at fertilisation or during the early stages of embryo development. Gamete formation differs significantly between males and females, affecting the incidence of aneuploid gametes, which is fourfold higher in females than in males. Molecular cytogenetic techniques have revealed the extent of full and mosaic aneuploidy in embryos created by in vitro fertilisation (IVF), explaining the high level of arrested development affecting these embryos. Maternal age is the most significant factor affecting the incidence of aneuploidy, but genetic anomalies in the parents are also important. Key Concepts Chromosomally abnormal conceptions are very high in humans, but the effects are lethal in almost all cases. Aneuploidy may arise at three developmental stages: during gamete formation, at fertilisation or during embryogenesis. Gamete formation (oogenesis or spermatogenesis) differs considerably between the sexes as males produce sperm throughout adult life, whereas females are born with a finite set of oogonia. These differences are reflected in the fourfold higher aneuploidy rate in females versus males. Maternal age is the most significant factor affecting the incidence of aneuploidy, but genetic variation, particularly chromosomal rearrangement, in a parent is also an important factor.

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Errors at mitotic segregation early in oogenesis and at first meiotic division in oocytes from donor females: Comparative genomic hybridization analyses in metaphase II oocytes and their first polar body

Cited by 26 publications

References 34 publications

Non-meiotic chromosome instability in human immature oocytes

Non-meiotic chromosome instability in human immature oocytes

Age-related increase in aneuploidy and alteration of gene expression in mouse first polar bodies

Origins of Human Aneuploidy

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