Pre fertilization DNA transfer to avoid mitochondrial disease inheritance appears safe

Transferring the nuclear genome from one egg into the cytoplasm of a donor egg is a strategy to enable women carrying mutations in their mitochondrial DNA to have healthy babies. A new study published in the open-access journal PLOS Biology, uses multiple "omics" techniques to show that this strategy, called spindle transfer, is likely to be safe, with little evidence of genetic or functional difference between the resulting embryos and healthy control in vitro fertilization (IVF) embryos. The results are likely to spur further adoption of spindle transfer for IVF when there is a risk of mitochondrial disease.

The "spindle" refers to the division apparatus that holds the nuclear chromosomes in suspension until fertilization. During spindle transfer, the maternal spindle is removed from an unfertilized egg and placed into a donor egg that has had its own spindle removed.Spindle transfer has been used clinically, but there remain questions about its safety.

To shed light on this question, the authors performed three different types of analyses on single cells from 23 blastocysts following spindle transfer and compared them to 23 control IVF blastocysts. They found no difference in DNA copy number, a measure of genomic integrity, between spindle transfer and control blastocysts. RNA expression profiles were also similar between the two blastocyst types, regardless of which layer of the blastocyst the cells were taken from.

The authors did find a small but significant reduction in the level of DNA demethylation in spindle transfer blastocysts in one layer, the trophectoderm, though not in two other layers. DNA demethylation is one of the processes used to increase gene expression during development, and their analysis suggested that the reduction was evidence of a slight delay in the process, rather than a permanent inability to upregulate the affected genes.