Mosaic results after preimplantation genetic testing for aneuploidy may be accompanied by changes in global gene expression

Aneuploidy in preimplantation embryos is a major cause of human reproductive failure. Unlike uniformly aneuploid embryos, embryos diagnosed as diploid-aneuploid mosaics after preimplantation genetic testing for aneuploidy (PGT-A) can develop into healthy infants. However, the reason why these embryos achieve full reproductive competence needs further research. Current RNA sequencing techniques allow for the investigation of the human preimplantation transcriptome, providing new insights into the molecular mechanisms of embryo development. In this prospective study, using euploid embryo gene expression as a control, we compared the transcriptome profiles of inner cell mass and trophectoderm samples from blastocysts with different levels of chromosomal mosaicism. A total of 25 samples were analyzed from 14 blastocysts with previous PGT-A diagnosis, including five low-level mosaic embryos and four high-level mosaic embryos. Global gene expression profiles visualized in cluster heatmaps were correlated with the original PGT-A diagnosis. In addition, gene expression distance based on the number of differentially expressed genes increased with the mosaic level, compared to euploid controls. Pathways involving apoptosis, mitosis, protein degradation, metabolism, and mitochondrial energy production were among the most deregulated within mosaic embryos. Retrospective analysis of the duration of blastomere cell cycles in mosaic embryos revealed several mitotic delays compared to euploid controls, providing additional evidence of the mosaic status. Overall, these findings suggest that embryos with mosaic results are not simply a misdiagnosis by-product, but may also have a genuine molecular identity that is compatible with their reproductive potential.

Automated summary

Aneuploidy in preimplantation embryos is a common cause of reproductive failure. Preimplantation genetic testing for aneuploidy (PGT-A) can identify embryos with mosaic patterns of diploid and aneuploid cells, which have the potential to develop into healthy infants. This study used RNA sequencing to compare gene expression profiles in different parts of blastocysts with varying levels of chromosomal mosaicism. The results showed that mosaic embryos have distinct gene expression patterns and pathways related to apoptosis, mitosis, protein degradation, metabolism, and mitochondrial energy production. Additionally, mosaic embryos exhibited mitotic delays compared to euploid controls. These findings suggest that embryos with mosaic results have a unique molecular identity that contributes to their reproductive potential.