Mosaicism in Preimplantation Human Embryos: When Chromosomal Abnormalities Are the Norm

Trends in Genetics

Volumn 33, Issue 7, 2017, Pages 448-463

  McCoy, Rajiv C ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

aneuploidy; fertility; mitosis; preimplantation genetic screening

Indexed keywords

ANEUPLOIDY; CELL CYCLE; CELL CYCLE CHECKPOINT; CHROMATID; CHROMOSOME ABERRATION; EMBRYO; GENETIC SCREENING; HUMAN; IN VITRO FERTILIZATION; MALIGNANT NEOPLASM; MEIOSIS; MITOSIS; MOSAICISM; OVARY; PREIMPLANTATION EMBRYO; PRIORITY JOURNAL; REVIEW; BLASTOCYST;

ANEUPLOIDY; BLASTOCYST; CHROMOSOME ABERRATIONS; HUMANS; MEIOSIS; MITOSIS; MOSAICISM;

EID: 85018275630     PISSN: 01689525     EISSN: 13624555     Source Type: Journal    
DOI: 10.1016/j.tig.2017.04.001     Document Type: Review

References (111)

1. Santaguida, S., Amon, A., Short-and long-term effects of chromosome mis-segregation and aneuploidy. Nat. Rev. Mol. Cell Biol. 16 (2015), 473–485.
2. Webster, A., Schuh, M., Mechanisms of aneuploidy in human eggs. Trends Cell Biol. 27 (2017), 55–68.
3. Treff, N.R., et al. SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH. Mol. Hum. Reprod. 16 (2010), 583–589.
4. Capalbo, A., et al. Detecting mosaicism in trophectoderm biopsies: current challenges and future possibilities. Hum. Reprod. 32 (2017), 492–498.
5. Munné, S., et al. Chromosome mosaicism in human embryos. Biol. Reprod. 51 (1994), 373–379.
6. Delhanty, J.D., et al. Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Hum. Genet. 99 (1997), 755–760.
7. Vanneste, E., et al. Chromosome instability is common in human cleavage-stage embryos. Nat. Med. 15 (2009), 577–583.
8. Baart, E.B., et al. Preimplantation genetic screening reveals a high incidence of aneuploidy and mosaicism in embryos from young women undergoing IVF. Hum. Reprod. 21 (2006), 223–233.
9. Mertzanidou, A., et al. Microarray analysis reveals abnormal chromosomal complements in over 70% of 14 normally developing human embryos. Hum. Reprod. 28 (2013), 256–264.
10. van Echten-Arends, J., Chromosomal mosaicism in human preimplantation embryos: a systematic review. Hum. Reprod. Update 17 (2011), 620–627.
11. McCoy, R.C., et al. Evidence of selection against complex mitotic-origin aneuploidy during preimplantation development. PLoS Genet., 11, 2015, e1005601.
12. Scott, R.T., Galliano, D., The challenge of embryonic mosaicism in preimplantation genetic screening. Fertil. Steril. 105 (2016), 1150–1152.
13. Braude, P., et al. Preimplantation genetic diagnosis. Nat. Rev. Genet. 3 (2002), 941–955.
14. Mastenbroek, S., et al. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum. Reprod. Update 17 (2011), 454–466.
15. Scott, R.T., et al. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil. Steril. 100 (2013), 624–630.
16. Adler, A., et al. Blastocyst culture selects for euploid embryos: comparison of blastomere and trophectoderm biopsies. Reprod. Biomed. Online 28 (2014), 485–491.
17. Gordon, D.J., et al. Causes and consequences of aneuploidy in cancer. Nat. Rev. Genet. 13 (2012), 189–203.
18. Barbash-Hazan, S., Preimplantation aneuploid embryos undergo self-correction in correlation with their developmental potential. Fertil. Steril. 92 (2009), 890–896.
19. Bielanska, M., et al. Chromosomal mosaicism throughout human preimplantation development in vitro: incidence, type, and relevance to embryo outcome. Hum. Reprod. 17 (2002), 413–419.
20. Braude, P., et al. Human gene expression first occurs between the four-and eight-cell stages of preimplantation development. Nature 332 (1988), 459–461.
21. Vassena, R., et al. Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development. Development 138 (2011), 3699–3709.
22. Zhao, R., et al. A nontranscriptional role for Oct4 in the regulation of mitotic entry. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 15768–15773.
23. Vera-Rodriguez, M., Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis. Nat. Commun., 6, 2015, 7601.
24. Yanez, L.Z., et al. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization. Nat. Commun., 7, 2016, 10809.
25. Harrison, R.H., et al. Lack of cell cycle checkpoints in human cleavage stage embryos revealed by a clonal pattern of chromosomal mosaicism analysed by sequential multicolour FISH. Zygote 8 (2000), 217–224.
26. Kiessling, A.A., et al. Evidence that human blastomere cleavage is under unique cell cycle control. J. Assist. Reprod. Genet. 26 (2009), 187–195.
27. Lee, A., Kiessling, A.A., Early human embryos are naturally aneuploid – can that be corrected?. J. Assist. Reprod. Genet. 34 (2016), 15–21.
28. Zhou, B.B.S., Elledge, S.J., The DNA damage response: putting checkpoints in perspective. Nature 408 (2000), 433–439.
29. Chavez, S.L., et al. Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage. Nat. Commun., 3, 2012, 1251.
30. Coonen, E., et al. Anaphase lagging mainly explains chromosomal mosaicism in human preimplantation embryos. Hum. Reprod. 19 (2004), 316–324.
31. Cahill, D.P., et al. Mutations of mitotic checkpoint genes in human cancers. Nature 392 (1998), 300–303.
32. van de Werken, C., Chromosome segregation regulation in human zygotes: altered mitotic histone phosphorylation dynamics underlying centromeric targeting of the chromosomal passenger complex. Hum. Reprod. 30 (2015), 2275–2291.
33. Wells, D., et al. Expression of genes regulating chromosome segregation, the cell cycle and apoptosis during human preimplantation development. Hum. Reprod. 20 (2005), 1339–1348.
34. Ganem, N.J., et al. A mechanism linking extra centrosomes to chromosomal instability. Nature 460 (2009), 278–282.
35. Vázquez-Diez, C., et al. Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 626–631.
36. Voet, T., et al. Breakage–fusion–bridge cycles leading to inv dup del occur in human cleavage stage embryos. Hum. Mutat. 32 (2011), 783–793.
37. Zhang, C.Z., et al. Chromothripsis from DNA damage in micronuclei. Nature 522 (2015), 179–184.
38. Daughtry, B.L., et al. Aneuploidy tolerance in rhesus macaque pre-implantation embryos via micronuclei formation, cellular fragmentation, and blastomere exclusion. Reprod. Fertil. Dev., 29, 2016, 110.
39. Sundvall, L., et al. Tetraploidy in hydatidiform moles. Hum. Reprod. 28 (2013), 2010–2020.
40. Newport, J., Kirschner, M., A major developmental transition in early Xenopus embryos: I. Characterization and timing of cellular changes at the midblastula stage. Cell 30 (1982), 675–686.
41. Mantikou, E., et al. Temporal and developmental-stage variation in the occurrence of mitotic errors in tripronuclear human preimplantation embryos. Biol. Reprod., 89, 2013, 42.
42. Katz-Jaffe, M.G., et al. Mitotic errors in chromosome 21 of human preimplantation embryos are associated with non-viability. Mol. Hum. Reprod. 10 (2004), 143–147.
43. Boveri, T., Zellen-Studien: Heft 4, Ueber die Natur der Centrosomen. 1900, Von Gustav Fischer.
44. Nam, H.J., et al. Centrosome dynamics as a source of chromosomal instability. Trends Cell Biol. 25 (2015), 65–73.
45. Manandhar, G., et al. Centrosome reduction during gametogenesis and its significance. Biol. Reprod. 72 (2005), 2–13.
46. Holubcová, Z., et al. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. Science 348 (2015), 1143–1147.
47. Schatten, H., Sun, Q.Y., The role of centrosomes in fertilization, cell division and establishment of asymmetry during embryo development. Semin. Cell Dev. Biol. 21 (2010), 174–184.
48. Habedanck, R., et al. The Polo kinase Plk4 functions in centriole duplication. Nat. Cell Biol. 7 (2005), 1140–1146.
49. McCoy, R.C., et al. Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos. Science 348 (2015), 235–238.
50. Zhang, Q., et al. Maternal common variant rs2305957 spanning PLK4 is associated with blastocyst formation and early recurrent miscarriage. Fertil. Steril. 107 (2017), 1034–1040.e5.
51. Sathananthan, A.H., Development of the human dispermic embryo. Hum. Reprod. Update 5 (1999), 553–560.
52. Ven, H.H., et al. Polyspermy in in vitro fertilization of human oocytes: frequency and possible causes. Ann. N. Y. Acad. Sci. 442 (1985), 88–95.
53. Chatzimeletiou, K., Spindle abnormalities in normally developing and arrested human preimplantation embryos in vitro identified by confocal laser scanning microscopy. Hum. Reprod. 20 (2005), 672–682.
54. Wirka, K.A., et al. Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development. Fertil. Steril. 101 (2014), 1637–1648.
55. Kalatova, B., et al. Tripolar mitosis in human cells and embryos: occurrence, pathophysiology and medical implications. Acta Histochem. 117 (2015), 111–125.
56. Zhan, Q., et al. Direct unequal cleavages: embryo developmental competence, genetic constitution and clinical outcome. PLoS One, 11, 2016, e0166398.
57. Hlinka, D., et al. Time-lapse cleavage rating predicts human embryo viability. Physiol. Res., 61, 2012, 513.
58. Brooker, A.S., Berkowitz, K.M., The roles of cohesins in mitosis, meiosis, and human health and disease. Methods Mol. Biol. 1170 (2014), 229–266.
59. Ishiguro, K.I., Watanabe, Y., Chromosome cohesion in mitosis and meiosis. J. Cell Sci. 120 (2007), 367–369.
60. Tachibana-Konwalski, K., Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes Dev. 24 (2010), 2505–2516.
61. Ottolini, C.S., et al. Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. Nat. Genet. 47 (2015), 727–735.
62. Chiang, T., et al. Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr. Biol. 20 (2010), 1522–1528.
63. Duncan, F.E., et al. Chromosome cohesion decreases in human eggs with advanced maternal age. Aging Cell 11 (2012), 1121–1124.
64. Cohen-Fix, O., Sister chromatid separation: falling apart at the seams. Curr. Biol. 10 (2000), R816–R819.
65. Jallepalli, P.V., et al. Securin is required for chromosomal stability in human cells. Cell 105 (2001), 445–457.
66. Zhang, N., et al. Overexpression of separase induces aneuploidy and mammary tumorigenesis. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 13033–13038.
67. Singh, V.P., Gerton, J.L., Cohesin and human disease: lessons from mouse models. Curr. Opin. Cell Biol. 37 (2015), 9–17.
68. Barber, T.D., et al. Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 3443–3448.
69. Sonoda, E., et al. Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev. Cell 1 (2001), 759–770.
70. Munné, S., et al. Treatment-related chromosome abnormalities in human embryos. Hum. Reprod. 12 (1997), 780–784.
71. Labarta, E., et al. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J. Clin. Endocrinol. Metab. 97 (2012), E1987–E1994.
72. Hong, K.H., Natural is not better: gonadotropin stimulation does not increase aneuploidy or diminish implantation rates of euploid embryos. Fertil. Steril. 106 (2016), e197–e198.
73. Jarvis, G.E., Estimating limits for natural human embryo mortality. F1000Res., 5, 2016, 2083.
74. Hertig, A.T., et al. Thirty-four fertilized human ova, good, bad and indifferent, recovered from 210 women of known fertility. Pediatrics 23 (1959), 202–211.
75. Sandalinas, M., Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage. Hum. Reprod. 16 (2001), 1954–1958.
76. Bielanska, M., Diploid–aneuploid mosaicism in human embryos cultured to the blastocyst stage. Fertil. Steril. 84 (2005), 336–342.
77. Vega, M., et al. Blastulation rates decline in a linear fashion from euploid to aneuploid embryos with single versus multiple chromosomal errors. Fertil. Steril. 102 (2014), 394–398.
78. Santos, M.A., et al. The fate of the mosaic embryo: chromosomal constitution and development of day 4, 5 and 8 human embryos. Hum. Reprod. 25 (2010), 1916–1926.
79. Rubio, C., et al. Impact of chromosomal abnormalities on preimplantation embryo development. Prenat. Diagn. 27 (2007), 748–756.
80. Ruangvutilert, P., et al. FISH analysis on day 5 post‐insemination of human arrested and blastocyst stage embryos. Prenat. Diagn. 20 (2000), 552–560.
81. Fragouli, E., The developmental potential of mosaic embryos. Fertil. Steril., 104, 2015, e96.
82. Greco, E., et al. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N. Engl. J. Med. 373 (2015), 2089–2090.
83. Gleicher, N., et al. Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos. Reprod. Biol. Endocrinol., 14, 2016, 54.
84. Bolton, H., et al. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nat. Commun., 7, 2016, 11165.
85. Carbone, L., Chavez, S.L., Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations. Syst. Biol. Reprod. Med. 61 (2015), 321–335.
86. Baffero, G.M., et al. Confined placental mosaicism at chorionic villous sampling: risk factors and pregnancy outcome. Prenat. Diagn. 32 (2012), 1102–1108.
87. Capalbo, A., et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum. Reprod. 29 (2014), 1173–1181.
88. Northrop, L.E., et al. SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts. Mol. Hum. Reprod. 16 (2010), 590–600.
89. Johnson, D.S., et al. Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass. Mol. Hum. Reprod. 16 (2010), 944–949.
90. Eggermann, T., et al. Mosaicism and uniparental disomy in prenatal diagnosis. Trends Mol. Med. 21 (2015), 77–87.
91. Engel, E., Uniparental disomy revisited: the first twelve years. Am. J. Med. Genet. 46 (1993), 670–674.
92. Besser, A.G., Mounts, E.L., Counselling considerations for chromosomal mosaicism detected by preimplantation genetic screening. Reprod. Biomed. Online 34 (2017), 369–374.
93. Biesecker, L.G., Spinner, N.B., A genomic view of mosaicism and human disease. Nat. Rev. Genet. 14 (2013), 307–320.
94. Maxwell, S.M., et al. Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing. Fertil. Steril. 106 (2016), 1414–1419.
95. Demko, Z.P., et al. Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. Fertil. Steril. 105 (2016), 1307–1313.
96. Delhanty, J.D., et al. Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridization (FISH). Hum. Mol. Genet. 2 (1993), 1183–1185.
97. Brezina, P.R., et al. Preimplantation genetic testing for aneuploidy: what technology should you use and what are the differences?. J. Assist. Reprod. Genet. 33 (2016), 823–832.
98. Johnson, D.S., et al. Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol. Hum. Reprod. 25 (2010), 1066–1075.
99. Handyside, A.H., et al. Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes. J. Med. Genet. 47 (2010), 651–658.
100. Fiorentino, F., et al. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil. Steril. 101 (2014), 1375–1382.
101. Treff, N.R., et al. Development and validation of an accurate quantitative real-time polymerase chain reaction-based assay for human blastocyst comprehensive chromosomal aneuploidy screening. Fertil. Steril. 97 (2012), 819–824.
102. Handyside, A.H., 24-Chromosome copy number analysis: a comparison of available technologies. Fertil. Steril. 100 (2013), 595–602.
103. Kane, S.C., et al. Pre-implantation genetic screening techniques: implications for clinical prenatal diagnosis. Fetal Diagn. Ther. 40 (2016), 241–254.
104. Sermon, K.D., et al. Detecting mosaicism in trophectoderm biopsies. Hum. Reprod. 32 (2017), 712–713.
105. Mamas, T., et al. Detection of aneuploidy by array comparative genomic hybridization using cell lines to mimic a mosaic trophectoderm biopsy. Fertil. Steril. 97 (2012), 943–947.
106. Hall, G.K., et al. Chromosomal microarray analysis allows prenatal detection of low level mosaic autosomal aneuploidy. Prenat. Diagn. 34 (2014), 505–507.
107. Spinella, F., et al. Next generation sequencing-based aneuploidy screening improves detection of low-level mosaicism in human embryos. Fertil. Steril. 102 (2014), e94–e95.
108. Goodrich, D., et al. A randomized and blinded comparison of qPCR and NGS-based detection of aneuploidy in a cell line mixture model of blastocyst biopsy mosaicism. J. Assist. Reprod. Genet. 33 (2016), 1473–1480.
109. Templado, C., et al. Aneuploidy in human spermatozoa. Cytogenet. Genome Res. 133 (2011), 91–99.
110. Gardner, R.L., Cockroft, D.L., Complete dissipation of coherent clonal growth occurs before gastrulation in mouse epiblast. Development 125 (1998), 2397–2402.
111. Garrisi, G., et al. Discordance among serial biopsies of mosaic embryos. Fertil. Steril., 106, 2016, e151.