A new single-cell study has found that aneuploidy is common in early-stage human embryos, a finding that may have implications for in vitro fertilisation approaches.
Aneuploidy is a leading cause of pregnancy loss and birth defects in humans, and in vitro fertilisation clinics often choose to discard embryos with aneuploidy rather than implanting them. It has been unclear how common chromosomal mosaicism is among human embryos.
Researchers at the John Hopkins University have now conducted a new study on aneuploidy and mosaicism using existing single-cell genomic data from human embryos. The study was reported in Genome Research earlier this week, where they found mitotic and meiotic aneuploidies in around 80% of embryos.
Senior author Rajiv McCoy said in a statement “clinicians have wrestled with the decision to transfer embryos featuring mosaic aneuploidy when no other embryos are available. In recent years, some have implanted such embryos and reported healthy births, indicating embryos may have resilience or self-correction of mosaicism”.
McCoy and his colleagues used previously published single-cell RNA sequencing data generated for more than 1000 cells from 74 human embryos. To detect aneuploidies, they looked for chromosome dosage-associated changes in gene expression and signatures for allelic imbalance. 80% of the embryos they studied had at least one aneuploid cell. Of which, 5% had only meiotic aneuploidies, which affect all embryonic cells and 49% had only mitotic aneuploidies which lead to mosaicism, and 26% had both types of aneuploidy.
The team also found that the rate of aneuploidy did not differ by cell type or day of differentiation. The researchers did find an enrichment of aneuploidy in the outer layer of trophectoderm cells rather than inner mass cells, but they noted a white confidence interval suggesting they could not rule out modest differences.
They also reported that nearly 3000 genes were differentially expressed between euploid and aneuploid cells, with upregulation of GDF15 in aneuploid cells compared to euploid cells being the most significant association.
With these findings, McCoy concludes that he hopes “we can move on from the debate about whether mosaicism is common or not, to understanding what features of mosaicism are associated with good or bad outcomes in pregnancy”.