Spindle Transfer Embryos in Humans Develop (Mostly) Normally

Spindle Transfer Embryos in Humans Develop (Mostly) Normally ...

According to recent research, one particular in vitro fertilization (IVF) technique for having a healthy baby appears to be safe for women with mitochondrial illnesses.

This technique, called spindle transfer, involves transferring the nuclear DNA from one of the woman's eggs into an enucleated donor egg that contains healthy mitochondria before being fertilized with sperm from a male partner. The new research combines single-cell multiomics techniques to demonstrate that this method produces embryos that are comparable to healthy controls created by standard IVF techniques.

Wei Shang, a physician at Beijing's Chinese PLA General Hospital, and Fuchou Tang, a PhD student at Peking University, Beijing, conducted the study, which has been published in PLoS Biology (Single-cell multiomics analyses of spindle-transferred human embryos suggests a mostly normal embryonic development).

When mitochondrial disease is at risk, a mitochondrial mutation may result in a myriad of metabolic, muscular, and neurologic problems. Only the maternal mitochondria, contained in the egg, are inherited in human reproduction. The findings from the new study are likely to encourage further adoption of spindle transfer for IVF when there is a risk of mitochondrial disease.

Mutations in mitochondrial DNA (mtDNA) are often associated with incurable illnesses and lead to detectable pathogenic variants in 1 out of 200 babies, according to the authors.

The removal of the link between mtDNA and the nuclear genome by spindle transfer (ST) might potentially prevent the transmission of mtDNA mutations from mother to offspring, according to the authors. The spindle refers to the apparatus that holds the chromosomes in place.

Spindle transfer has been used in the clinical setting, but concerns remain about its safety. Until now, no systematic omics investigation had been undertaken in human embryos.

The researchers used single cells from blastocystsballs of cells that formed after fertilization. The blastocyst stage is the final in vitro development stage of assisted reproductive technology (in vitro fertilization and embryo transfer) [which is why] we selected human blastocysts to perform single-cell multiomics analyses.

They compared cells from 23 blastocysts that formed following spindle transfer to cells from 23 control IVF blastocysts and found no difference in DNA copy number (a measure of genomic integrity) or RNA expression profiles.

In one layer, the trophectoderm, the researchers found a modest but significant decrease in DNA demethylation, although not in two other layers. DNA demethylation is one of the processes used to boost gene expression during development.

Tang believes that the reduction may be due to a minor delay in the process rather than a permanent inability to upregulate the affected genes. After the blastocyst stage, spindle transfer embryos may recover enough DNA demethylation before implantation [in the uterine wall].

However, the scope of the research was a bit restricted. According to the authors, more embryos, more developmental stages, and more aspects of embryo biology should be studied in the future.

According to the researchers, safety is one of the most important factors bringing ST to the clinic. [Our] work provides the first comprehensive set of molecular evidence supporting the theory that ST is generally safe in human embryos and requires further scientific evaluations and clinical testing.

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