Egg cells made with DNA from human skin fertilised in the lab

Human embryos have been developed from eggs given the DNA of adult skin cells – a feat that had been previously achieved in mice. This could one day provide a way to gay couples or women with fertility problems to have children biologically linked to both parents.

Scientists already know how to reproduce animals in cloning. This implies replacing the nucleus of an egg, which is filled with genetic material, by that of a body cell, like a skin cell. But apart from the legal limitations concerning human cloning, many couples want babies with a mixture of their two genes, which requires sperm and an egg, explains Shoukhrat Mitalipov at Oregon Health and Science University.

To move on this subject is difficult because the eggs and sperm are haploid, which means that they bear only one set of chromosomes instead of the usual two. The challenge is therefore half of the complete set of chromosomes present in cells such as skin cells – after selecting a healthy mixture of original genes, as is generally happening in nature.

The girls develop all their eggs while being in the uterus, where the progenitors of the egg cells – which originally contain 46 chromosomes – go through an elaborate process of duplication, mixing and division to make 23 chromosomes.

Mitalipov wondered if he could imitate this process in his laboratory by taking advantage of the natural chemical processes which promote such a division in mature human eggs, before and during fertilization.

After having succeeded in this subject with the mouse, he and his colleagues have now tested the approach in a test at the start of the stage with people. They first withdrew the nuclei from hundreds of eggs that were given by healthy women. These eggs were arrested in a precise phase of their development associated with the chromosomal division. Then, the nuclei of the skin cells called fibroblasts of a healthy voluntary woman were placed in these eggs. The images taken through a microscope show the chromosomes aligned on the pins, the scaffolding in the cells to separate the chromosomes.

Then the team injected the sperm of a healthy donor to fertilize some of the eggs. This is an approach similar to that used to make babies using the mitochondrial DNA of a third person, which is sometimes done to reduce the risk of certain genetic conditions.

This injection normally triggers an egg to finalize its selection of chromosomes and eliminate double DNA in preparation to receive more sperm. But in eggs derived from the skin, this process has stalled, aligned chromosomes but never separating. Thus, the researchers tried again with a new set of fertilized eggs, this time using electrical pulses which allow calcium to rush into the egg – simulating a natural signal triggered when a sperm contacts the outside of the egg – and incubating the eggs with a drug that extinguishes them from the inactive state in which they are generally found before fertilization.

During a series of tests, the researchers finally carried out eggs which half reduced their number of chromosomes, by eliminating those additional. At the end of the experience, 9% of fertilized eggs had become blastocysts – a ball of cells which forms around five or six days after fertilization, which is generally what is transferred to the uterus during IVF. The researchers did not try such a transfer or maintained blastocysts beyond six days.

But the mixture of genes that constituted the remaining chromosomes seemed particularly subject to defects. “I think this approach is currently far too immature to be taken into account for a clinical application,” said Mitinori Saitou at the University of Kyoto in Japan.

Katsuhiko Hayashi at the University of Osaka in Japan agrees, finding the “very sophisticated and well -organized” method but “too ineffective and risky for immediate clinical application”. Nevertheless, Hayashi says that the team made “a significant breakthrough in the reduction of half of the human genome”. “New technologies will come from this achievement,” he says.

Mitalipov says that the criticisms are correct, adding that his team strives to overcome the problem of faults. “The main thing is that we are somehow halfway, but not exactly where we have to be,” he says.