Scientists are a step closer to making IVF eggs from patients’ skin cells after adapting the procedure that created Dolly the sheep, the first cloned mammal, more than two decades ago.
The work raises the prospect of older women being able to have children who share their DNA, and to overcome common forms of infertility caused by a woman’s eggs becoming damaged by disease or cancer treatment.
The radical procedure, which may take a decade to perfect and approve in humans, would also enable male couples to have genetically related children, since the men’s DNA could be combined in the fertilised egg and carried to term by a surrogate mother.
“Should this technology become clinically viable in the future, it holds the potential to revolutionise IVF and offer hope to many infertile patients who have lost gametes due to disease, ageing or cancer treatments,” said Aleksei Mikhalchenko, the first author on the study, at Oregon Health and Science University in Portland, US. Gametes are sperm and egg cells.
Shoukhrat Mitalipov, a senior author on the study, said his lab had spent the past 20 years developing fertility treatments for patients who lack healthy sperm or eggs. Existing options, he said, forced people to use donated sperm or eggs and have genetically unrelated children. “Our technology would enable infertile patients to have genetically related children, providing a path to parenthood that is currently unavailable even with IVF,” he said.
Scientists around the world are working on several approaches to create eggs and sperm in the lab. Last year, Japanese researchers created eggs from the skin cells of male mice, leading to the birth of mouse pups with two fathers. Other teams hope to create sperm and eggs from embryonic stem cells, which are versatile enough to form any tissue in the body.
While many countries, including the UK, outlaw the use of artificial sperm and eggs to treat infertile couples, advances in the coming years may drive calls to permit the procedures if they are deemed safe and effective.
The latest experiments, published in Science Advances, were performed in mice and took a different, much swifter approach to creating IVF eggs. The researchers start with a donor egg and remove its nucleus. They then transfer in the nucleus from a mouse skin cell. The egg is then cultured in such a way that it naturally discards half of its chromosomes. This crucial step ensures the egg contains the correct number of chromosomes – half from each parent – once it is fertilised with a sperm. “Eggs can be made by our approach in a matter of two to three hours,” said Mikhalchenko.
Dolly the sheep was created in 1996 through a similar process, known as somatic cell nuclear transfer, or SCNT. Prof Ian Wilmut and his team at the Roslin Institute in Edinburgh extracted the nucleus from a mammary gland cell of a Finn Dorset ewe and fused it with an egg, producing an embryo that carried all of the ewe’s DNA.
Mitalipov’s team announced in 2022 the birth of three live mice from their experiments, but the success rate was less than 1%. Their latest study focuses on how the eggs discard half of their chromosomes, which is necessary for them to develop into a healthy embryo. “Our current objective is to enhance the success rate at each stage of the process,” Mitalipov said.
Paula Amato, a professor of obstetrics and gynaecology, and a co-author on the study, said the advantage of the team’s technique was that it avoided the long culture times used by other approaches that reprogram cells. “Over several months, a lot of harmful genetic and epigenetic changes can happen,” she said.
“While the clinical applications of this technology may still be a decade away and will require thorough evaluation of safety, efficacy and ethical aspects, its potential to address fertility-related issues offers promising prospects for future reproductive medicine,” Mikhalchenko added.
