Fertilization in vitro increases non-disjunction during early cleavage divisions in a mouse model system

Bean, Christopher J.; Hassold, Terry; Judis, LuAnn; Hunt, Patricia A.

doi:10.1093/humrep/17.9.2362

Cited by 71 publications

(45 citation statements)

References 27 publications

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“…In the mouse, the addition of folliclestimulating hormone during in vitro maturation of oocytes, or simply IVF itself, increased the incidence of aneuploidy in meiosis I. 24,25 Further work comparing the incidence and pattern of meiotic errors following different stimulation regimes, including mild stimulation and natural cycle IVF, as well as analysis of the meiotic origin of aneuploid IVF pregnancies may identify improved clinical strategies to reduce the incidence of aneuploidy in these women and perhaps increase the success rates of IVF.…”

Section: Discussionmentioning

confidence: 99%

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

147

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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: Discussionmentioning

confidence: 99%

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

147

View full text Add to dashboard Cite

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“…In the case of IVF, the post-retrieval ageing prior to fertilization may also compromise the meiotic process (Eichenlaub-Ritter, 1998). Recent studies on mice have also suggested that slight alterations of in vitro conditions might exacerbate a predisposing risk to nondisjunction (Ohno et al, 2001;Bean et al, 2002). Disturbances of the meiotic process do not seem to delay the anaphase onset (Hodges et al, 2002) which suggests that in oogenesis of older women, the regulatory checkpoint mechanisms that monitor both the spindle assembly and chromosome movements, could also be particularly ineffective (LeMaire-Adkins et al, 1997; Steuerwald et al, 2001).…”

Section: Maternal Age Effectmentioning

confidence: 99%

Effect of maternal age on the frequency of cytogenetic abnormalities in human oocytes

Pellestor

Anahory

Hamamah

2005

Cytogenet Genome Res

104

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The cytogenetic investigation of human oocytes was initiated in the Sixties, and for the last four decades, this field of research has never stopped progressing as new technologies appear. Numerous karyotyping studies and molecular cytogenetic studies have been reported to date, providing a large body of data on the incidence and the distribution of chromosomal abnormalities in human female gametes, but also displaying a great variability in results, which may be essentially attributable to the technical limitations of these in situ methods when applied to human oocytes. Essentially, the most relevant analyses have led to the estimate that 15–20% of human oocytes display chromosome abnormalities, and they have emphasized the implication of both whole chromosome nondisjunction and chromatid separation in the occurrence of aneuploidy in human oocytes. The effect of advanced maternal age on the incidence of aneuploidies has also been investigated in human oocytes. Most previous studies have failed to confirm any relationship between maternal age and aneuploidy frequency in human oocytes, whereas the more recent reports based on large samples of oocytes or polar bodies have provided evidence for a direct correlation between increased aneuploidy frequency and advanced maternal age, and have clarified the contribution of the various types of malsegregation in the maternal age-dependent aneuploidies.

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“…Therefore, the most commonly studied model used to investigate the impact of assisted reproductive technologies (ART) on chromosomal defects, in both oocytes and preimplantation embryos, has been the mouse (14). However, since the overall incidence of aneuploidy (trisomy or monosomy) among mouse oocytes does not exceed 1-2%, it is not a suitable translational animal model (15).…”

Section: Introductionmentioning

confidence: 99%

Chromosomal instability in rhesus macaque preimplantation embryos

Dupont

Froenicke

Lyons

et al. 2009

Fertility and Sterility

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Objective-To establish a relevant animal model to systematically investigate chromosomal instability in human oocytes and preimplantation embryos. Design-Prospective rhesus monkey IVF study.Setting-Academic laboratory, Oregon National Primate Research Center and Caribbean Primate Research Center. Patients-Young Rhesus macaque females.Interventions-In vitro produced (IVP) entire rhesus macaque preimplantation embryos were cytogenetically assessed using a 5-color fluorescent in situ hybridization (FISH) assay developed for rhesus macaque chromosomes homologous to human chromosomes 13, 16, 18, X and Y, using human bacterial artificial chromosome (BAC) probes.Main Outcome Measure(s)-Chromosomal abnormality rates in preimplantation embryos from young rhesus macaque females were established.Result(s)-Fifty preimplantation embryos, displaying good morphology and normal development, from 11 young rhesus macaque females were analyzed. Overall, 27 embryos (54%) were normal, 11 embryos (22%) mosaic, 3 embryos (6%) chaotic, 2 embryos (4%) aneuploid, 3 embryos (6%) haploid and 4 embryos (8%) triploid. Conclusion(s)-These data indicate that IVP rhesus macaque and human preimplantation embryos exhibit similar numerical chromosomal aberrations. Rhesus macaques appear to be a suitable animal model for investigating the origin of chromosomal instability observed in human preimplantation embryos.

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Fertilization in vitro increases non-disjunction during early cleavage divisions in a mouse model system

Cited by 71 publications

References 27 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

Effect of maternal age on the frequency of cytogenetic abnormalities in human oocytes

Chromosomal instability in rhesus macaque preimplantation embryos

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