The new technique treats infertility by turning a skin cell into an egg that is capable of producing viable embryos.
The method could allow same-sex couples, women of advanced maternal ages and those unable to produce viable eggs to produce healthy offspring with genetic influences from both parents.
A research team from the Oregon Health & Science University (OHSU) documented in vitro gametogenesis, or IVG, in mice through the preliminary steps of their new technique, which relies upon transferring the nucleus of a skin cell into a donated egg with its nucleus removed.
The researchers then modified the skin cell’s nucleus to reduce its chromosomes by half, so that it could then be fertilized by a sperm cell to create a viable embryo.
Biologist Dr. Shoukhrat Mitalipov, a senior author of the study and director of the OHSU Center for Embryonic Cell and Gene Therapy, explained: "The goal is to produce eggs for patients who don’t have their own eggs."
The study, published in the journal Science Advances, paves the way for older women and those unable to produce eggs due to cancer or other medical treatments to be able to produce babies.
It also raises the prospect of men in same-sex relationships being able to have children genetically related to both parents.
Instead of attempting to differentiate induced pluripotent stem cells (iPSCs) into sperm or egg cells, the OHSU researchers honed a method based on somatic nuclear transfer, in which a skin cell nucleus is transplanted into a donor egg stripped of its nucleus.
In 1996, scientists in Scotland famously used this technique to clone Dolly the sheep from the cells of one parent.
However, the OHSU researchers described the result of a technique that resulted in embryos with chromosomes contributed by both parents.
The process they carried out first involved the researchers transplanting the nucleus of a mouse skin cell into a mouse egg that is stripped of its own nucleus.
The implanted skin cell nucleus discards half of its chromosomes, prompted by cytoplasm - the liquid that fills cells - within the donor egg.
The process is similar to meiosis, in which cells divide to produce mature sperm or egg cells.
This is the key step, resulting in a haploid egg with a single set of chromosomes.
The researchers then fertilize the new egg with sperm in a process called 'in vitro fertilization'; creating a diploid embryo with two sets of chromosomes - which would ultimately result in healthy offspring with equal genetic contributions from both parents.
The research team had previously demonstrated the proof of their concept in a study published in January 2022, but their new study goes further by meticulously sequencing the chromosomes.
The researchers found that the skin cell’s nucleus segregated its chromosomes each time it was implanted in the donor egg and, in rare cases, this happened perfectly, with one from each pair of matching egg and sperm chromosomes.
“This publication basically shows how we achieved haploidy,” Dr. Mitalipov said.
“In the next phase of this research, we will determine how we enhance that pairing so each chromosome pair separates correctly.”
Whilst labs around the world are involved in IVG techniques that involve a time-intensive process of reprogramming skin cells to become iPSCs and then differentiating them to become egg or sperm cells, the OHSU team say they are missing this step out.
“We’re skipping that whole step of cell reprogramming,” co-author Dr Paula Amato, a professor of obstetrics and gynecology in the OHSU School of Medicine, said.
“The advantage of our technique is that it avoids the long culture time it takes to reprogram the cell.
"Over several months, a lot of deleterious genetic and epigenetic changes can happen.”
Although researchers are also studying the technique in human eggs and early embryos, Dr Amato added that it would likely be years before the technique would be ready for clinical use.
“This gives us a lot of insight,” she said.
“But there is still a lot of work that needs to be done to understand how these chromosomes pair and how they faithfully divide to actually reproduce what happens in nature."
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