March 28, 2023

The technique used to create biparental mice will be applied to humans in up to 10 years

published on 16/03/2023 06:00

    (credit: Antony Mwangi/Revelation)

(credit: Antony Mwangi/Revelation)

In an article published in the journal Nature, geneticist Katsuhiko Hayashi details how he produced functional eggs by converting stem cells from two male mice into female and male gametes. Last week, Hayashi, a researcher at Japan’s Kyushu University, announced the results of the experiment in person at a scientific conference in England.

Male and female gametes—sperm and eggs, respectively—are produced by a type of stem cell known as primordial germ cells. Their differentiation into gametes requires the proper functioning of the sex chromosomes.

Previous research investigating the possibility of changing the sex of germ cells found that gamete production was reduced or produced structures with low fertility. Now, Hayashi’s team reports that using pluripotent stem cells (including embryonic and induced) can produce more functional eggs.

The authors took skin cells from the tail of mature male mice (with XY chromosomes) and transformed them into induced pluripotent stem cells. These constructs were cultured in vitro, a process that results in the loss of the Y chromosome in approximately 6% of the total sample, generating XO cells.

seven descendants

Further growing these XO cells in culture caused the X chromosome to double. According to the researchers, treating them with reversin, a drug that interferes with cell division, increased the efficiency of the process. The resulting structures, with two X chromosomes, were then induced to differentiate into primordial germ cells and then into eggs. When fertilized and implanted in the uterus of a mouse, they produced viable offspring. About 1% of embryos produced offspring (seven out of 630).

The authors note that a more rigorous evaluation of the impact of this male-to-female cell conversion method on genome integrity will be needed for future research and applications. Last week, during the event in England, Hayashi said that, at least in technological terms, there is a possibility of replicating the technique with human cells within 10 years.

In an interview with the Guardian last week, George Daly, dean of Harvard Medical School in the United States, called the project “exciting”, adding that previous research had shown that creating human gametes in the laboratory was more difficult than they thought. made with mouse cells. “We still don’t understand enough of the unique biology of human gametogenesis to replicate Hayashi’s challenging work in mice,” he told the British paper.

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