March 23, 2024

Scientists move step closer to making IVF eggs from skin cells

Researchers at Oregon Health & Science University have developed a promising technique for creating artificial eggs.

In the journal Science Advances they described the process: they transferred the nucleus of a skin cell into a donated egg whose nucleus has been removed. Experimenting in mice, researchers coaxed the skin cell’s nucleus into reducing its chromosomes by half, so that it could then be fertilized by a sperm cell to create a viable embryo.

“The goal is to produce eggs for patients who don’t have their own eggs,” said senior author Shoukhrat Mitalipov,director of the OHSU Center for Embryonic Cell and Gene Therapy.

The technique, called in vitro gametogenesis, could be used by women of advanced maternal age or for those who are unable to produce viable eggs due to previous treatment for cancer or other causes. It also raises the possibility of men in same-sex relationships having children who are genetically related to both dads, one supplying an artificial egg, the other the sperm.

Rather than attempting to differentiate induced pluripotent stem cells, or iPSCs, into sperm or egg cells, OHSU researchers are focused on a technique based on somatic cell nuclear transfer, in which a skin cell nucleus is transplanted into a donor egg stripped of its nucleus. In 1996, researchers famously used this technique to clone a sheep in Scotland named Dolly.

In that case, researchers created a clone of one parent. In contrast, the OHSU study described the result of a technique that resulted in embryos with chromosomes contributed from both parents. The process involves three steps:

  • Researchers transplant the nucleus of a mouse skin cell into a mouse egg that is stripped of its own nucleus.
  • Prompted by cytoplasm — liquid that fills cells — within the donor egg, the implanted skin cell nucleus discards half of its chromosomes. The process is similar to meiosis, when 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.
  • Researchers then fertilize the new egg with sperm, a process called in vitro fertilization. This creates a diploid embryo with two sets of chromosomes — which would ultimately result in healthy offspring with equal genetic contributions from both parents.

Laboratories around the world are involved in a different technique of IVG. But it involves a time-intensive process of reprogramming skin cells to become iPSCs, and then differentiating them to become egg or sperm cells.

“We’re skipping that whole step of cell reprogramming,” said co-author Paula Amato, of the OHSU School of Medicine. “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, Amato said it will be years before the technique would be ready for clinical use.