Informativity of blastocentesis in the evaluation of chromosomal mosaicism at the blastocyst stage

Actuality: Phenomenon of chromosomal mosaicism often recorded the in human embryos at the preimplantation stage of development. This may be due to features of chromosome segregation at this stage of ontogenesis. The use of extracellular DNA from the intracavitary fluid may contribute to the study of the frequency and mechanisms of occurrence of chromosomal mosaicism in the blastocyst. This is achieved by molecular karyotyping of cells undergoing apoptosis and inaccessible for karyotyping using traditional technologies of cytogenetic studies. Objective: Evaluation the frequency of chromosomal mosaicism in human embryos at the blastocyst stage. Materials and Methods: CGH-analysis of 14 human embryos on day 5 of a division of the inner cell mass, trophectoderm and blastocoel fluid. Results: Comparative analysis of karyotypes of embryoblast and trophoblast of 14 blastocysts revealed that mosaicism in each embryo is observed on average in five chromosomes. Additional use of cell-free DNA leads to increase of spectrum of mosaic chromosomal abnormalities to 7 per sample. Analysis of molecular karyotypes using extracellular DNA proves the predominant elimination of embryoblast cells with autosomal monosomy. Conclusions: The use of extracellular DNA from the cavity of the blastocyst increases the frequency of chromosomal mosaicism registration in the cycles of in vitro fertilization and preimplantation genetic diagnosis. This is accomplished primarily due to the identification of aneuploidies presented in the inner cell mass of the blastocyst.

бластоцентез, внеклеточная ДНК, хромосомный мозаицизм, внутриполостная жидкость бластоцисты, внутренняя клеточная масса, трофэктодерма, cell-free DNA, chromosomal mosaicism, blastocysts intracavitary fluid, embryoblast, trophectoderm

1. Артюхова В.Г., Лебедев И.Н., Маркова Е.В., Светлаков А.В. Структура числовых хромосомных нарушений и особенности их фенотипических эффектов на преимплантационных этапах развития человека. Медицинская генетика. 2009; 8(2): 19-24.

2. van Echten-Arends J., Mastenbroek S., Sikkema-Raddatz B. et al. Chromosomal mosaicism in human preimplantation embryos: a systematic review. Hum Reprod Update. 2011; 17(5): 620-627.

3. Liu J., Wang W., Sun X. et al. DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic. Biology of Reproduction. 2012; 87(6): 148, 1-9

4. Rius M., Daina G., Obradors A. et al. Comprehensive embryo analysis of advanced maternal age-related aneuploidies and mosaicism by short comparative genomic hybridization. Fertil. Steril. 2011; 95(1): 413-416.

5. Palini S., Galluzzi L., De Stefani S. et al. Genomic DNA in human blastocoele fluid. Reprod. Biomed. Online. 2013;26(6): 603-610.

6. Bolton H., Graham S.L., Van der Aa N. et al. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nat Commun. 2016; 7: 11165.