Eggs produced from male stem cells lead to creation of mice with two fathers

Dr Emma Green

Progress Educational Trust

13 March 2023

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[BioNews, London]

Egg cells have been generated from male mouse cells and, once fertilised and implanted into female mice, have developed seemingly healthy, fertile offspring.

The research was presented at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London, by Professor Katsuhiko Hayashi, now at Osaka University, Japan. However, the work has yet to be published in a peer-reviewed journal. This early, proof-of-concept technique could assist with some types of infertility and, if able to overcome a number of technical and ethical barriers, could eventually lead to children with two biological fathers.

'This is the first case of making robust mammal oocytes [egg cells] from male cells,' Professor Hayashi said in his presentation.

The original aim of the research was to address infertility in women with Turner syndrome who only have one X chromosome, since egg development requires two X chromosomes. The researchers chose to use male cells which have an X and a Y chromosome, since the Y chromosome is smaller, and can be lost naturally when cells are grown in the lab.

The process first involved turning male mouse skin cells into induced pluripotent stem cells (iPSCs), which have the potential to develop into almost any type of cell. They then extracted the cells which had naturally lost the Y chromosome. The researchers then used a technique to generate cells with two X chromosomes. By providing a mixture of signals, they were able to turn the XX iPSCs into immature eggs. The eggs were then fertilised with mouse sperm and the embryos were transferred to the uterus of female mice.

The mouse pups generated from this technique were healthy, grew normally, and were fertile adults. However, the success rate was low, with only seven pups developing from 630 transferred embryos.

'The trick of this, the biggest trick, is the duplication of the X chromosome,' said Professor Hayashi. 'We really tried to establish a system to duplicate the X chromosome.'

During his speech, Professor Hayashi confirmed that much work still needs to be undertaken and that any medical applications of this work are still a long way off. The research team are currently comparing the mice generated from this technique to those bred using conventional methods.

'There are big differences between a mouse and the human,' said Professor Hayashi. He explained that these differences can complicate the transfer of research from the lab to the clinic, in particular because egg and embryo development takes much longer in humans than in mice.

'If you're going to apply this in humans, you really want to err on the side of safety, caution and efficiency,' Professor Keith Latham, a developmental biologist at Michigan State University (who was not involved in the research) told New Scientist.

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