A new study from Oregon Health & Science University explains the science behind a promising strategy for treating infertility by transforming a skin cell into an egg capable of creating healthy embryos.
Researchers at OHSU documented in vitro gametogenesis, or IVG, in a mouse model using the earliest steps of a procedure that involves transplanting the nucleus of a skin cell into a donated egg with the nucleus removed. In mouse experiments, researchers forced the nucleus of a skin cell to reduce its chromosomes by half, allowing it to be fertilized by a sperm cell and produce a healthy embryo.
The work was published today in the journal Science Advances.
“The goal is to produce eggs for patients who don’t have their own eggs,” explained senior author Shoukhrat Mitalipov, Ph.D., head of the OHSU Center for Embryonic Cell and Gene Therapy.
The procedure could be employed by women of advanced maternal age or those who are unable to produce healthy eggs due to previous cancer treatment or other factors. It also increases the chances of men in same-sex partnerships having children who are genetically connected to both parents.
Rather than attempting to develop induced pluripotent stem cells, or iPSCs, into sperm or egg cells, OHSU researchers are focusing on a process known as somatic cell nuclear transfer, which involves transplanting a skin cell nucleus into a donor egg that has had its nucleus removed. In 1996, researchers notably utilized this technique to clone Dolly, a sheep from Scotland.
In such situation, researchers made a clone of one parent.
In contrast, the OHSU study detailed the outcome of a procedure that produced embryos with chromosomes from both parents. The procedure consists of three steps:
Researchers insert the nucleus of a mouse skin cell into a mouse egg that has been stripped of its own nucleus.
The implanted skin cell nucleus discards half of its chromosomes in response to cytoplasm, which is the liquid that fills cells within the donor egg. The process is comparable to meiosis, in which cells split to form mature sperm or egg cells. This is the critical phase, which yields a haploid egg with a single pair of chromosomes.
Researchers then use sperm to fertilize the new egg, a process known as in vitro fertilization. This produces a diploid embryo with two sets of chromosomes, which will eventually result in healthy kids with equal genetic contributions from both parents.
OHSU researchers already showed the proof of concept in a report published in January 2022, but the latest work takes it a step further by methodically sequencing the chromosomes.
The researchers discovered that the skin cell’s nucleus separated its chromosomes each time it was placed in the donor egg. In other cases, this worked perfectly, with one from each pair of matching egg and sperm chromosomes.
“This publication basically shows how we achieved haploidy,” Mitalipov added. “In the next phase of this research, we will determine how we enhance that pairing so each chromosome-pair separates correctly.”
Laboratories throughout the world are working on a new type of IVG that includes a time-consuming procedure of reprogramming skin cells to become iPSCs and then differentiating them to become egg or sperm cells.
Although researchers are also investigating the procedure in human eggs and early embryos, Amato believes it will be years before it is suitable for practical usage.
“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.”