高達百分之58囊胚染色體有鑲嵌化現象

morula期胚胎高達80%染色體有mosaic現象
blastocyst期胚胎高達58%染色體有mosaic現象

http://humrep.oxfordjournals.org/content/25/8/1916.full

The fate of the mosaic embryo: chromosomal constitution and development of Day 4, 5 and 8 human embryos

1. Margarida Avo Santos1,*†, 
2. Gijs Teklenburg1,†, 
3. Nick S. Macklon1,2,
4. Diane Van Opstal3, 
5. G. Heleen Schuring-Blom4, 
6. Pieter-Jaap Krijtenburg4,
7. Johanna de Vreeden-Elbertse1, 
8. Bart C. Fauser1 and 
9. Esther B. Baart1,5

+Author Affiliations

1. ¹Department of Reproductive Medicine and Gynaecology, University Medical Centre, Utrecht, The Netherlands
2. ²Department of Obstetrics and Gynaecology, Division of Developmental Origins of Health and Disease, Princess Anne Hospital, University of Southampton, Southampton, UK
3. ³Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands
4. ⁴Department of Medical Genetics, Division of Biomedical Genetics, University Medical Centre, Utrecht, The Netherlands
5. ⁵Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands

1. *Correspondence address. E-mail: mavoribe@umcutrecht.nl

• Received February 17, 2010.
• Revision received April 14, 2010.
• Accepted April 21, 2010.

 

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Abstract

BACKGROUND Post-zygotic chromosome segregation errors are very common in human embryos after in vitro fertilization, resulting in mosaic embryos. However, the significance of mosaicism for the developmental potential of early embryos is unknown. We assessed chromosomal constitution and development of embryos from compaction to the peri-implantation stage.

METHODS From 112 cryopreserved Day 4 human embryos donated for research, 21 were immediately fixed and all cells were analysed by fluorescent in situ hybridization (FISH) for chromosomes 1, 7, 13, 15, 16, 18, 21, 22, X and Y. The remaining 91 embryos were thawed, with 54 embryos undergoing biopsy of one or two cells which were fixed and analysed by FISH. Biopsied embryos were kept in standard culture conditions for 24 h. Embryos arrested before cavitation (n = 24) were fixed whereas developing Day 5 blastocysts (n = 24) were co-cultured for a further 72 h on an endometrial monolayer followed by fixation. Cell numbers were counted and all nuclei were analysed by FISH. Data from a previous FISH analysis on cryopreserved good-quality Day 5 blastocysts (n = 36) were also included in the present study.

RESULTS FISH analysis was successful for 18 Day 4 fixed embryos and, according to our definition, 83% were mosaic and 11% showed a chaotic chromosomal constitution. FISH analysis of two blastomeres from Day 4 developing embryos showed that 54% were mosaic, 40% were normal and 6% were abnormal. Analysis of Day 4, 5 and 8 whole embryos showed a decrease in incidence of mosaicism over time, from 83% on Day 4 to 42% on Day 8. A significant positive correlation was observed between the total cell number and the percentage of normal cells in developing Day 5 and Day 8 embryos but not in developing Day 4 or embryos arrested before cavitation.

CONCLUSIONS These data suggest that both the developmental arrest of a significant proportion of mosaic embryos on Day 4, and the cell death or reduced proliferation of aneuploid cells within an embryo may be responsible for the observed decrease of aneuploid blastomeres from compaction to the peri-implantation stage.

Figure 3

Incidence of mosaicism on Days 4, 5 and 8 post-fertilization. Percentage of Day 4 morulas, embryos arrested before cavitation, developing Day 5 blastocysts and Day 8 peri-implantation embryos, diagnosed as normal, mosaic, chaotic and uniformly abnormal after FISH analysis of chromosomes 1, 7, 13, 15, 16, 18, 21, 22, X and Y.