Fertilizable human eggs created from skin cells using the technique that cloned Dolly the sheep

For many women, the main cause of infertility is the lack of functioning eggs, especially after the age of 35, when quality begins to decline dramatically. If techniques to stimulate the production of a woman’s own eggs fail, the only option is to use donated eggs, but that means giving up the chance to have offspring with one’s own DNA. On Tuesday, a study led by Shoukhrat Mitalipov’s laboratory at Oregon Health & Science University (OHSU) in the U.S. shows a path by which science could overcome this limitation and even open the door for same-sex couples to have children with the genetics of both partners.

For years, scientists have been seeking radical alternatives to conventional reproduction. One approach is the laboratory transformation of skin or blood cells into eggs or sperm. In mice, fertilizable eggs and sperm have been produced that can fertilize and give rise to offspring, but achieving this in humans is much more difficult.

One of the teams working in this field is led by the Japanese scientist Mitinori Saitou. He seeks to produce reproductive cells following a path similar to the natural one. First, adult cells are reprogrammed using four genes that rewind them to a pluripotent stem cell state, capable of becoming any cell in the body. These malleable cells are then transformed into primordial germ cells and finally into eggs or sperm. This final achievement has been reached in mice, but has not yet been reproduced in humans.

In the study published Tuesday in Nature Communications by Mitalipov and Paula Amato’s team, an alternative approach is presented. Instead of creating an egg from scratch, it attempts to reprogram an adult skin cell to mimic what happens during meiosis. This process begins with a normal cell containing 46 chromosomes — 23 inherited from the father and 23 from the mother — and generates our own reproductive cells, eggs and sperm, which have only 23 chromosomes. During this process, the genes shuffle like a deck of cards, producing half the inheritance of a new, unique individual.

What the U.S. team demonstrates is that it is possible to induce a reductive cell division, like that which occurs in meiosis, so that a skin cell with 46 chromosomes becomes a functional egg with 23. In women, this complex process normally takes more than a decade, beginning when they are still an embryo.

The researchers used a technique known as Somatic Cell Nuclear Transfer (SCNT), the same method used for cloning that made Dolly the sheep possible in 1996. Researchers took the nucleus of a skin cell, with its 46 chromosomes, and introduced it into a donor egg from which the nucleus had previously been removed. If that egg were fertilized with sperm, it would produce an embryo with three sets of chromosomes, which would be nonviable. To avoid this, they induced a process they called mitomeiosis, which tricks the cell into dividing without first duplicating its DNA, discarding one set of chromosomes and making the egg functional.

Using this process, they produced 82 functional oocytes, which were then fertilized in the laboratory. Of these eggs, only 9% developed to six days — the stage at which the embryo would be transferred to the uterus in an in vitro fertilization procedure — but in the experiment, the culture was not continued, and the embryos were discarded.

Promising proof of concept

The success, however, is presented only as a proof of concept, showing that it is possible to do, although many challenges remain. Besides the fact that few embryos reached the stage at which they would be implantable, the process produced embryos with abnormalities due to missing or extra chromosomes, or mosaics where some cells were normal and others had trisomies.

Nuria Martí, first author of the study, believes that “this new approach in the field of in vitro gametogenesis is promising,” but acknowledges that much work remains. “Among other things, we need to understand how homologous chromosomes pair to create oocytes with the correct number of chromosomes, force chromosomal recombination, and also imprinting [the epigenetic marks that silence certain genes depending on whether they come from the father or the mother and make the embryo viable],” she explains. “In my opinion, it will take at least 10 years before this technique is ready for clinical trials.”

In statements reported by the specialized website Science Media Center, Ying Cheong, professor of reproductive medicine at the University of Southampton, believes that, although this is an early laboratory study, “in the future it could transform how we understand infertility and miscarriage and perhaps one day open the door to creating egg- or sperm-like cells for those who have no other options.”

For Martí, the most exciting aspect of this study is that it offers people who otherwise cannot the chance to have a genetically related child. This applies to “women who do not have oocytes due to age or other reasons, such as previous cancer treatment, [...] or same-sex couples having children genetically related to both parents.”

In 2013, Shoukhrat Mitalipov became a global science star when he announced that he had obtained human embryonic stem cells through nuclear transfer, the same technique used now. At that time, his team reprogrammed an adult skin cell by inserting it into an egg from which the nucleus had previously been removed. The resulting egg, containing the skin donor’s DNA, was activated and developed into a blastocyst, at which point the stem cells were extracted.

This success demonstrated his mastery of the SCNT technique, the same foundation of the work published. That method had worked in several animals, from goats and cows to macaques, but never in humans. The finding caused a stir at the time because it represented a step toward human cloning. Mitalipov clarified that the purpose of his work was to obtain stem cells to fight diseases in the future, and denied that his goal was ever to clone humans.

Sign up for our weekly newsletter to get more English-language news coverage from EL PAÍS USA Edition