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Pronuclear Transplantation Shows Promise, Challenges

A Wellcome Trust Center for Mitochondrial Research-led team has conducted preclinical studies on pronuclear transplantation, studying some 525 eggs from 64 women, as it reports in Nature this week.

Such a 'three-person' embryo in which the nuclear genetic material of a fertilized egg is transferred to a nucleus-less, but mitochondria-containing donor egg would enable women with mitochondrial disease to have a genetically related child, the Guardian notes. Mitochondrial replacement therapy was legalized last year in the UK.

As techniques used in proof-of-concept studies involving abnormally fertilized human zygotes did not work in normal fertilized human zygotes, the Wellcome Trust Center for Mitochondrial Research's Mary Herbert and her colleagues tested an alternative approach for transplanting pronuclei. They transplanted pronuclei after the end of meiosis instead of just before the first mitotic division.

Through this early pronuclear transplantation approach — taking place some eight hours after insemination — the researchers found they could get early-stage embryos containing less than 5 percent mutated mitochondrial DNA, as the Guardian reports.

The researchers also examined gene expression patterns, mtDNA-encoded oxidative phosphorylation expression patterns, and other aspects of these embryos to find no difference between them and ones generated via traditional IVF routes.

"The key message is that we have found no evidence the technique is unsafe. Embryos created by this technique have all the characteristics to lead to a pregnancy," co-author Doug Turnbull, the director of the Center for Mitochondrial Research, tells Reuters.

However, since some defective mitochondrial DNA is carried over, the researchers point out that the approach reduces, but does not eliminate the risk of mitochondrial disease. "It sounds a note of caution for us," Turnbull tells New Scientist.

The Guardian notes that Columbia University's Dieter Egli reported a similar problem last month. He found that, on occasion, those mutated maternal mitochondria outcompete the healthy replacement mitochondria, defeating the purposed of the procedure.