Mitotic spindle disruption in human preimplantation embryos activates the spindle assembly checkpoint but not apoptosis until Day 5 of development

Jacobs, Kurt; Velde, H. Van de; Paepe, Caroline De; Sermon, Karen; Spits, Claudia

doi:10.1093/molehr/gax007

Cited by 31 publications

(21 citation statements)

References 37 publications

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“…In other words, in up to day-4 preimplantation embryos, aneuploid blastomeres can continue cell division resulting in aneuploid daughter cells. However, when reaching the blastocyst stage, there is a drastic change in the embryo's cell cycle control, and the spindle assembly checkpoint becomes able to induce apoptosis, in agreement with what has been reported in the mouse (19,20). A condition of mosaicism could be a possible consequence in the attempt of aneuploidy correction, and the chances that mosaic embryos have to further develop are strictly related to the proportion of euploid/aneuploid cells, to the type of abnormalities involved, and to the efficiency of the corrective mechanisms (21)(22)(23).…”

Section: Discussionsupporting

confidence: 88%

“…Whereas in the TE, aneuploid cells exhibit increased cell cycle length and senescence for which they tend to be outcompeted by euploid cells, in inner cell mass they are preferentially eliminated by apoptosis (19). A similar mechanism acts in humans, by which apoptosis occurs more frequently in aneuploid cells in the attempt made by the embryo to recover a euploid, viable condition (20,24). The blastocoelic cavity, a closed compartment where DNA and proteins of embryonic origin accumulate (3,25,26), could represent a sort of collector for different cell products, including those generated by apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Deoxyribonucleic acid detection in blastocoelic fluid: a new predictor of embryo ploidy and viable pregnancy

Magli¹,

Albanese²,

Crippa³

et al. 2019

Fertility and Sterility

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To investigate blastocysts, defined as euploid and aneuploid by trophectoderm (TE) cell analysis, for the presence of DNA in the blastocoelic fluid (BF) detected by whole-genomic amplification (WGA); and to correlate the presence of DNA in BF with the clinical outcome after the transfer of TE-euploid blastocysts. Design: Retrospective study. Setting: In vitro fertilization unit. Patient(s): This study included 91 patients performing preimplantation genetic testing for aneuploidy on TE cells from January 2015 to December 2017. In the case of ET, only single blastocyst transfers were performed. Intervention(s): Blastocoelic fluids and TE cells were retrieved from 256 blastocysts before vitrification. All blastocysts were diagnosed by array-comparative genomic hybridization (a-CGH) on TE cells. Amplification and a-CGH of DNA from BFs was performed at a later time after TE biopsy and ET. Main Outcome Measure(s): Whole-genomic amplification of BFs, evaluation of the chromosome condition in BFs and TE cells, and correlation of BF results with the clinical outcome of TE-euploid transferred blastocysts. Result(s): The incidence of amplification after WGA was significantly lower in BFs from TE-euploid blastocysts (n ¼ 32, 45%) when compared with the aneuploid ones (n ¼ 150, 81%), resulting in 182 BFs with successful DNA amplification. When submitted to a-CGH, informative results were obtained from 172 BFs. Comparison of these results with those from the corresponding TE cells gave a ploidy concordance of 93.6% and a mean number of aneuploid events per sample that was higher in BFs than in TE cells (2.0 vs. 1.4, respectively). After the transfer of 53 TE-euploid blastocysts, the clinical pregnancy rate was 77% in the group with BF-failed amplification, and 37% after BF-successful amplification. The same trend was found for the ongoing pregnancy rate (68% vs. 31.5%, respectively). Conclusion(s): The presence of DNA in BFs detected by WGA is correlated with the blastocyst ploidy condition defined by TE cell biopsy and with the implantation potential of TE-euploid blastocysts. These findings could have a clinical implication for the selection of the most viable embryo for transfer because, after submitting BFs to WGA, priority would be given to TE-euploid blastocysts with BFfailed amplification. Similarly, BF-failed amplification could be an additional selection criterion to prioritize embryos for transfer even in conventional IVF cycles with blastocysts that were vitrified after BF aspiration. (Fertil Steril Ò 2019;111:77-85. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Deoxyribonucleic acid detection in blastocoelic fluid: a new predictor of embryo ploidy and viable pregnancy

Magli¹,

Albanese²,

Crippa³

et al. 2019

Fertility and Sterility

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“…This is in agreement with our observation that BMP4‐treated embryos show a morphologically normal appearance comparable with the control embryos until blastulation. Although the apoptotic machinery is present throughout the development (Exley et al, ; Spanos et al, ), apoptosis seems to be suppressed before compaction and/or differentiation (Brison & Schultz, ; Byrne et al, ; Jacobs et al, ; Long et al, ). This observation is intriguing and different possible explanations have been proposed.…”

Section: Discussionmentioning

confidence: 99%

BMP4 plays a role in apoptosis during human preimplantation development

Paepe

Aberkane

Dewandre

et al. 2018

Molecular Reproduction Devel

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Comprehensive understanding of lineage differentiation and apoptosis processes is important to increase our knowledge of human preimplantation development in vitro. We know that BMP signaling is important for different processes during mammalian development. In mouse preimplantation embryos, BMP signaling has been shown to play a role in the differentiation into extra‐embryonic trophectoderm (TE) and primitive endoderm (PE). In this study, we aimed to investigate the effect of bone morphogenetic protein 4 (BMP4) supplementation on human preimplantation embryos cultured in vitro. The BMP4 treatment impaired human blastocyst formation. No differences in the expression of the early lineage markers NANOG, CDX2, GATA3, and GATA6 were found between BMP4‐treated embryos and controls. Instead, BMP4 supplementation triggered apoptosis in the human blastocyst. We focused on P53, which is known to play a major role in the apoptosis. In BMP4‐treated embryos, the P53 responsive gene expression was not altered; however, the P53 deacetylase SIRT1 was downregulated and acetylated P53 was increased in mitochondria. Altogether, our findings suggest that BMP4 plays a role in the apoptosis during human preimplantation development.

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“…It is also unclear how stable microtubule kinetochore attachments and biorientation are established and controlled during the oocyte to embryo transition. From the available studies of mouse and human embryos, it seems that the SAC components are present and in principle functional during preimplantation cleavages [70,71]. Moreover, the SAC effector proteins, Bub3, Mad2, and BubR1, are essential for early embryogenesis as null mutants of these components die at very early stages of embryogenesis [72–74].…”

Section: The Sac and Cell Cycle Control At The Oocyte To Embryo Transmentioning

confidence: 99%

Mysteries in embryonic development: How can errors arise so frequently at the beginning of mammalian life?

Schneider

Ellenberg

2019

PLoS Biol

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Chromosome segregation errors occur frequently during female meiosis but also in the first mitoses of mammalian preimplantation development. Such errors can lead to aneuploidy, spontaneous abortions, and birth defects. Some of the mechanisms underlying these errors in meiosis have been deciphered but which mechanisms could cause chromosome missegregation in the first embryonic cleavage divisions is mostly a “mystery”. In this article, we describe the starting conditions and challenges of these preimplantation divisions, which might impair faithful chromosome segregation. We also highlight the pending research to provide detailed insight into the mechanisms and regulation of preimplantation mitoses.

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Mitotic spindle disruption in human preimplantation embryos activates the spindle assembly checkpoint but not apoptosis until Day 5 of development

Abstract: This work was supported by the Fund for Scientific Research Flanders (Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen) and the Methusalem grant to Karen Sermon of the Research Council of the Vrije Universiteit Brussel. The authors declare no competing financial interests.

Cited by 31 publications

References 37 publications

Deoxyribonucleic acid detection in blastocoelic fluid: a new predictor of embryo ploidy and viable pregnancy

Deoxyribonucleic acid detection in blastocoelic fluid: a new predictor of embryo ploidy and viable pregnancy

BMP4 plays a role in apoptosis during human preimplantation development

Mysteries in embryonic development: How can errors arise so frequently at the beginning of mammalian life?

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