In 2018, a team of Chinese researchers succeeded in obtaining mice from same-sex parents. But while rodents conceived from two mothers were viable, offspring from two fathers (and a surrogate mother) died 48 hours after birth. A Japanese team has overcome this obstacle with an entirely different approach, producing viable oocytes from only male cells.
The experiment, published in Nature on March 15, had been presented a week earlier (ironically on March 8, International Women’s Rights Day) at the Third International Summit on Human Genome Editing in London.
Katsuhiko Hayashi (Kyushu University, Fukuoka, and Osaka University) and his colleagues drew on a decade of work on gametogenesis, the formation of male (sperm) and female (oocyte) sex cells. In this case, the latter were produced from male cells. The Japanese team took advantage of a phenomenon that is generally a handicap when cells are cultured in vitro: the spontaneous loss of chromosomes, in particular the Y present in male cells, coupled with the X (female cells have two X chromosomes).
Katsuhiko Hayashi started with adult cells taken from the tails of male mice (XY), treated to become pluripotent stem cells, ie capable of differentiating into any cell type. In vitro, during their divisions, some cells (about 6%) lost their Y chromosome. The cells in question, known as X0, were then placed in a medium containing reversin, a molecule that disrupts division, which induced the duplication of the X chromosome. These XX cells could then be cultivated together with fetal ovarian cells, constituting a favorable medium for their transformation into oocytes. These could then be fertilized in vitro to produce embryos, which were implanted in surrogate mothers.
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In the end, out of 630 embryos implanted, seven led to the birth of mice that, Katuhiko Hayashi said, “seem to grow normally to adulthood,” a success rate of 1.1%.
For Jonathan Bayerl and Diana Laird (University of California, San Francisco) who commented on this work in Nature, it “opens up new perspectives in reproductive biology and fertility research.” First of all, for basic research, by producing mouse lines with a stable genetic background, much like identical twins. “This could also offer a way to save endangered species from a single male, provided that a carrier female of the same or related species is available to carry the embryos to term,” they added. Incidentally, Katsuhiko Hayashi is involved in a program to save the white rhinocerosthe problem in this case being that only two females of this species remain.
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