Home Medizin Wissenschaftler verwandeln Hautzellen bei Mäusen in funktionsfähige Eier

Wissenschaftler verwandeln Hautzellen bei Mäusen in funktionsfähige Eier

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Recent research from Oregon Health & Science University describes the science behind a promising technique for treating infertility, where a skin cell is transformed into an egg cell capable of producing viable embryos.

Researchers at OHSU documented in vitro gametogenesis (IVG) in a mouse model through the preparatory steps of a technique based on transferring the nucleus of a skin cell into a donated egg cell whose nucleus has been removed. Through experiments in mice, the researchers induced the skin cell nucleus to reduce its chromosomes by half, allowing it to then be fertilized by a sperm cell to create a viable embryo.

The study is published today in the journal Science Advances.

“The goal is to produce eggs for patients who do not have their own eggs,” said senior author Shoukhrat Mitalipov, Ph.D., Director of the OHSU Center for Embryonic Cell and Gene Therapy.

The technique could be used by women of advanced maternal age or women unable to produce viable eggs due to previous cancer treatment or other reasons. It also increases the possibility for men in same-sex relationships to have children genetically related to both parents.

Instead of attempting to differentiate induced pluripotent stem cells (iPSCs) into sperm or egg cells, OHSU researchers focus on a technique based on somatic cell nuclear transfer, where a skin cell nucleus is transplanted into a donor egg whose nucleus has been removed. This technique was famously used in 1996 to clone a sheep named Dolly in Scotland.

In this case, the researchers created a clone of one parent.

On the contrary, the OHSU study described the outcome of a technique leading to embryos with contributed chromosomes from both parents. The process involves three steps:

  • Researchers transplant the nucleus of a mouse skin cell into a mouse egg whose nucleus has been removed.
  • Triggered by cytoplasm – the fluid that fills cells – within the donor egg, the implanted skin cell nucleus discards half of its chromosomes. This process is similar to meiosis, where cells divide to produce mature sperm or egg cells. This is the crucial step leading to a haploid egg cell with a single set of chromosomes.
  • Researchers then fertilize the new egg cell with sperm, a process known as in vitro fertilization. This results in a diploid embryo with two sets of chromosomes – ultimately leading to healthy offspring with equal genetic contributions from both parents.

OHSU researchers have already demonstrated proof of concept in a study published in January 2022, but the new study goes further by sequencing the chromosomes meticulously.

The researchers found that the skin cell nucleus separated its chromosomes each time it was implanted into the donor egg. In rare cases, this process occurred perfectly, with one matching pair of egg and sperm chromosomes from each pair.

“This publication essentially shows how we have achieved haploidy,” said Mitalipov. “In the next phase of this research, we will determine how to enhance this pairing so that each pair of chromosomes separates correctly.”

Laboratories worldwide are involved in a different IVG technique that includes a time-consuming process of reprogramming skin cells into iPSCs and differentiating them into egg or sperm cells.

“We are skipping all that cell reprogramming step. The advantage of our technique is that it avoids the long culture time required for cell reprogramming. Over several months, many harmful genetic and epigenetic changes can occur.”

Paula Amato, Professor of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University

Although researchers are also studying the technique on human eggs and early embryos, according to Amato, it will take years before the technique is ready for clinical use.

“This gives us a lot of insights,” she said. “But there is still much work to be done to understand how these chromosomes pair and how they accurately divide to actually reproduce what happens in nature.”


Oregon Health & Science University

Journal Reference:

Mikhalchenko, A., et al. (2024) Induction of somatic cell haploidy through premature cell division. Science Advances. doi.org/10.1126/sciadv.adk9001.

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