Chromosome instability frequently occurs in human malignant solid tumors and is a hallmark of tumorigenesis, but has not been identified in other biological processes. A large number of studies have reported mosaic whole-chromosome imbalances, and there have been sporadic reports on rare segmental aneuploidies in human in vitro–fertilized embryos; these findings suggest that chromosome instability could also occur during human embryogenesis. There are few data on chromosomal imbalances in embryos from normal fertile women. No comprehensive studies have investigated genomic imbalances during embryogenesis.
The aim of this study was to investigate embryonic chromosome instability in cleavage-stage embryos and its frequency, nature, and consequences. The investigators developed 2 new array-based approaches to analyze the genomes of single cells used in combination to increase the accuracy of copy-number variation detection. This methodology was used to study the genomic constitution of all available blastomeres from good-quality embryos from young women (<35 years old) without indications for preimplantation genetic aneuploidy screening who were undergoing in vitro fertilization for genetic risks unrelated to fertility.
The data revealed a high frequency of chromosome instability in most cleavage-stage embryos involving complex patterns of segmental chromosomal imbalances and mosaicism for whole-chromosome aneuploidies and uniparental disomies. Frequent segmental deletions, duplications, and amplifications were uncovered that were reciprocal in sister blastomeres, indicating the occurrence of breakage fusion-bridge cycles. These patterns were reminiscent of the chromosomal instabilities previously identified in human cancers and the complex chromosomal aberrations observed in birth defects.
These findings show that chromosome instability is prevalent early in human embryogenesis. The data suggest that postzygotic chromosome instability may be a leading cause of constitutional chromosomal disorders.